What is nanotechnology?
• Nanotechnology is often defined as "technology at the nanoscale."
• However, understanding this requires defining the concept of the
nanoscale itself.
• Terms like "nanofiber" also indicate this scale; anything with
"nano" implies nanoscale.
• Without a clear definition of the nanoscale, the concept of
nanotechnology remains incomplete.
• Another concise definition is "engineering with atomic precision"
(APT).
• However, this definition lacks the emphasis on "fundamentally
new properties" that nanotechnologists stress.
What is nanotechnology?
• The US National Nanotechnology Initiative emphasizes working at the
molecular level to create new structures.
• Nanotechnology focuses on materials and systems with significantly
enhanced properties at the nanoscale.
• The US Foresight Institute highlights nanotechnology's control at the
nanometer scale to produce novel materials and devices.
• Functionality is emphasized in the design, synthesis, and application
of nanomaterials and devices.
• Nanotechnology deals with materials where structures smaller than
100 nm are essential for functionality.
• Control distinguishes nanotechnology from chemistry, emphasizing
deliberate manipulation at the nanoscale.
• A comprehensive definition sees nanotechnology as the application
of scientific knowledge to manipulate materials at the nanoscale.
History of
nanotechnology
• Richard Feynman's 1959 lecture at Caltech, titled "There's Plenty of Room
at the Bottom," laid the foundation for nanotechnology.
• Feynman envisioned machines constructing smaller machines, ultimately
reaching the atomic scale.
• He offered a $1000 prize for building a working electric motor no larger
than 1/64th of an inch, which was achieved by William McLellan using
conventional techniques.
• Marvin Minsky proposed a similar idea, emphasizing the potential of small
machines fabricating elements at high rates.
• The concept of the assembler, a universal nanoscale assembling machine,
was elaborated by Eric Drexler, with the potential to exponentially increase
manufacturing capability.
• James Clerk Maxwell's 1871 invention of the "demon," selectively allowing
molecules to pass through a door, can be considered an early concept in
nanotechnology, intertwining physics with information.
History of
nanotechnology
• Nanoparticles have a long history dating back to Greco-Roman times, evidenced by Lead
sulphide (PbS) nanocrystals -PbS nanocrystals used to color hair black.
• Gold nanoparticles, utilized in medicine, have historical significance, including John
Utynam's patent for stained glass incorporating nanoparticulate gold in 1449.
• Paracelsus administered gold nanoparticles to patients in the early sixteenth century for
certain ailments, akin to modern therapeutic applications of magnetic nanoparticles.
• The advanced metallurgical properties of Damascus swords, made over 400 years ago,
have been attributed to embedded carbon nanotubes.
• Nanoparticles currently hold significant commercial importance within nanotechnology.
• Chemical methods for fabricating nanoparticles were established by the middle of the
nineteenth century, such as Thomas Graham's method for producing ferric hydroxide
nanoparticles.
• Wolfgang Ostwald extensively lectured on nanoparticles in the early twentieth century,
contributing to the field's knowledge.
• Departments of colloid science existed in many universities until the mid-twentieth
century, overlapping with heterogeneous catalysis, where fineness of division correlated
with increased specific activity.
BIOLOGY AS
PARADIGM
• Cells, the smallest viable unit of life, contain intricate
machinery at smaller scales, evidenced by molecular
biology research.
• Biological machinery, such as molecule carriers, enzymes,
motors, and pumps, serves various functions within cells.
• Drexler's schema of nanoscale assemblers drew inspiration
from biological machinery, indicating the feasibility of
constructing artificial devices at a similar scale.
• The biological nanoparadigm's most practical
manifestation is self-assembly, a process well-known in the
nonliving world, but more sophisticated in nature.
• Programmable self-assembly, observed in nature and
inspired by virologists' work, allows for the precise
specification of final structures using components that
interlock in specific ways and can change structure upon
binding.
• Programmable self-assembly offers a potential
manufacturing route for nanodevices, bridging the gap
between nanoscopic products and macroscopic artifacts.
WHY NANOTECHNOLOGY?
• Nanotechnology offers several distinct advantages:
• Novel combinations of material properties can be created.
• Nanoscale devices require less material, energy, and
consumables, leading to enhanced function and
accessibility.
• Nanotechnology provides a universal fabrication
technology, potentially leading to the development of
personal nanofactories.
• Human motivations, such as the desire to explore the
unexplored and to conquer nature, also contribute to the
development of nanotechnology.
• Opportunities for traditional conquests of nature at the
macroscopic scale are limited, leading to exploration at the
nanoscale.
• Nanotechnology can offer immediate benefits through product
substitution or incremental improvement, particularly in
industries like space exploration.
NOVEL COMBINATIONS OF
PROPERTIES
• two methods for creating nanomaterials exist:
adding nanoadditives to a matrix and fabricating
materials atom-by-atom.
• Adding nanoadditives to a matrix can enhance
material properties, such as strength or
conductivity.
• Fabricating materials atom-by-atom is more
expensive but offers unique properties due to
nanoscale effects.
• As matter is downscaled, certain properties
change qualitatively, such as optical absorption
spectra and melting points.
• Nanoscale materials can exhibit different
behaviors due to factors like confinement of
electrons and increased surface area.
• Chemists have observed that finely divided
heterogeneous catalysts are more active due to
increased surface area.
Nanoscale
•
The nanoscale is typically defined as ranging from 1 to 100
nanometers, although exact limits are debated.
•
Consensus on the definition of the nanoscale simplifies discussions and
facilitates understanding of nanotechnology.
•
Nanotechnology involves manipulating materials at the nanoscale to
exploit unique functional properties.
•
As size decreases below 100 nm, qualitatively new features emerge, a
fundamental aspect of nanotechnology.
•
Length is prioritized in defining the nanoscale, likely due to historical
measurement practices.
•
The prefix "nano" derives from the Greek "νανoσ," meaning "dwarf,"
and is formalized as the multiplier 10-9 in the S.I. unit system.
•
One nanometer (1 nm) equals 10-9 meters, slightly larger than the size
of an individual atom.
SYNTHESIS OF
NANOPARTICLES
• Nanostructure synthesis methods are categorized into "top-down" and
"bottom-up" approaches.
• Top-down methods start with large objects and reduce their dimensions
to the nanoscale.
• Bottom-up methods start from atomic or molecular levels to produce
nanoparticles, which may then be assembled into larger structures.
• Synthesis methods are further classified into physical and chemical
methods.
• Physical methods include ball milling, evaporation, sputtering, chemical
vapor deposition, etc.
• Chemical methods include sol-gel, chemical bath deposition,
hydrothermal, sonochemical, etc.
• Additionally, lithographic techniques are discussed for generating
nanostructure patterns.
Bottom-Up Approaches
CHAPTER 4
Physical Vapor
Deposition
• Technique for thin film
formation.
• Utilizes a target to transfer
source material onto
substrate surface.
• Dominated by physical
methods; no chemical
reactions occur.
• Can be categorized based on
procedure.
Evaporation
• Traditional method for thin film
preparation.
• Often considered the foundation of
thin film synthesis.
• Simple process involving vaporizing
the source material in a low-pressure
vacuum chamber.
• Material grows on substrate
connected to a holder.
• Key parameter: Vapor pressure
controlled by heating the source.
Evaporation
• Transport Phenomenon
• Occurs straightforwardly due to large
mean free path compared to targetsubstrate distance.
• Main limitation: Uniform film growth
over large areas.
• Modifications:
• Use of multiple sources.
• Substrate rotation.
• Loading source and substrate on
a sphere's surface.
Evaporation
• Molecular Beam Epitaxy (MBE)
• Modified evaporation technique
for single crystal growth.
• Similar to evaporation but under
ultrahigh vacuum conditions.
• Molecular beams generated by
heating solid materials in Knudsen
cells.
• Cells aligned radially with
substrate.
Advantages of Molecular Beam
Epitaxy (MBE):
Negligible Contamination:
Ultrahigh vacuum ensures minimal contamination, leading to high purity films.
In Situ Characterization:
In situ tools like XPS, AES, RHEED can be attached for real-time monitoring and characterization without
disturbing the process.
Single Crystal Substrate:
Utilization of single crystal substrates enables precise control over crystal orientation and quality.
Individual Source Control:
Enables independent control over evaporation rates of different sources, facilitating complex material
compositions.
Slow Growth Rate:
Allows for precise control over film thickness and quality.
Low Growth Temperature:
Facilitates growth at lower temperatures, preserving material properties and reducing defects.
Hyperabrupt Surface Formation:
Leads to sharp interfaces between layers, crucial for device performance.
Precise Control for 2D Layer Growth:
Enables the growth of atomically thin 2D layers with high precision.
Sputtering
• Sputtering is a widely trusted PVD process used for thin
film deposition, etching, and analytical purposes.
• The basic setup includes a target (cathode), anode
(substrate), and a sputtering medium.
• Energetic particles bombard the target, transferring
material into the gas phase.
• Sputtering occurs when the kinetic energy of incoming
particles exceeds conventional thermal energies (~1 eV).
• A glow discharge ignites with the target as the cathode
and the substrate as the anode, facilitating sputtering.
• One of the main advantages of sputtering is its universal
applicability, as it can sputter any material.
• Argon is commonly used as the sputtering gas.
• Two main sputtering techniques exist: DC sputtering and
Radio Frequency (RF) sputtering.
• Introduction to Chemical Vapor Deposition (CVD):
• Chemical Vapor Deposition (CVD) is distinct from PVD
processes as it involves chemical reactions.
• In CVD, reactions occur in the gas phase, resulting in a
nonvolatile solid deposited as a thin film on a suitable
substrate.
• Types of CVD Methods:
1. Thermal Activation:
1. Requires high temperatures (>900 °C).
2. Used for conventional CVD processes.
3. Organometallic components can operate at
lower temperatures, known as Metal-Organic
CVD (MOCVD).
Chemical Vapor
Deposition
2. Plasma Activation:
1. Operates at lower temperatures (300–500 °C).
2. Known as Plasma-Enhanced CVD (PECVD).
3. Plasma is excited by RF or microwave energy.
3. Photon Activation:
1. Involves direct activation of reactants in the
presence of shortwave ultraviolet radiation.
2. Enables precise control over deposition
processes.
Chemical Vapor
Deposition
•
Flexibility of Chemical Vapor Deposition (CVD):
•
CVD allows synthesis of specific solids from various precursors
by adjusting their concentration and composition.
•
Different films can be obtained by varying precursor
composition and temperature.
•
CVD enables the generation of various morphologies, unlike
PVD, without requiring ultrahigh vacuum chambers.
•
Factors Influencing CVD Processes:
•
Despite being a nonequilibrium process, equilibrium analysis
is essential to understand CVD intricacies.
•
Reactions in CVD are governed by the first and second laws of
thermodynamics, predicting reaction feasibility, kinetics, and
associated energies.
•
The geometry of the reactor and chamber pressure are
crucial. Pressure is typically maintained at 0.01 atmospheres,
but low-pressure CVD operates in the range of 0.5–1 Torr.
•
Types of CVD Reactors:
•
CVD reactors can be classified into hot wall and cold wall
types.
•
Hot wall reactors: Tubular in shape with resistive heating.
•
Cold wall reactors: Inductive heating is applied to the
substrate using graphite susceptors, while the walls remain
cold with air/water flow.
Atomic Layer Deposition
(ALD)
• LD is a newly introduced technology, representing a modified version of CVD.
• ALD offers precise control over the growth mechanism, allowing for self-limiting
growth.
• Its unique self-limiting growth nature enables the creation of mono or few-layer
films, including 2D or nearly 2D films.
• ALD Mechanism:
• ALD mechanism combines vapor phase self-assembly and surface reaction.
• Surface activation occurs through chemical reaction, followed by the introduction
of precursor molecules into the chamber.
• Precursor molecules react with the activated surface, forming chemical bonds with
the substrate.
• Notably, precursor molecules do not react with each other, leading to the
formation of a monolayer.
• Further activation of the monolayer can result in the formation of additional layers,
allowing for the generation of complex films.
Chemical Methods
Sol–Gel
Introduction to Sol-Gel Technique:
The sol-gel technique is a versatile method for synthesizing various materials at a low cost.
It is commonly used for producing ceramic coatings and nanoparticles, offering control
over properties such as surface area, pore volume, and grain size.
Basic Principles of Sol-Gel Technique:
The sol-gel process involves hydrolysis and polycondensation reactions, typically using
tetraethyl orthosilicate (TEOS) as a precursor.
A "sol" refers to a stable dispersion of colloidal particles or polymers in a solvent, while a
"gel" consists of a three-dimensional network enclosing a liquid phase.
Sol-gel processes can be categorized as aqueous-based or alcohol-based, depending on
the presence of water during the reaction. Non-hydrolytic sol-gel processes also exist,
which do not require a solvent.
Precursor materials are often metal alkoxides, such as metal(RO)x, where M represents
the metal, R represents the alkyl group, and x is the valence state of the metal.
Chemical Methods
Homogeneous Gel Formation:
• To achieve homogeneous coatings or monodispersed nanoparticles via the sol-gel
process, it's crucial to obtain a homogeneous gel without precipitation.
• Precipitation can occur due to physical agglomeration or chemical reactions
between alkoxides and water or chelating agents, leading to the formation of
insoluble hydroxides or organic salts.
• Additives may be used to extend the gelation time and enhance the stability of
sol-gel products.
Basic Sol-Gel Reaction:
• The sol-gel reaction involves dispersed colloidal particles with negligible
gravitational force, exhibiting random Brownian motion within the fluid matrix.
• Short-range forces such as Van der Waals attraction and surface charges
dominate the interaction among particles, counteracted by repulsive forces.
• Depending on the formation of the network structure, gels are classified as
colloidal or polymeric gels.
Chemical Methods
• Colloidal Gels vs. Polymeric Gels:
• Colloidal gels are formed from sol particles through aggregation
and condensation, creating a three-dimensional network
surrounded by a liquid phase.
• Also known as corpuscular gels, colloidal gels are characterized by
the formation of networks from colloidal particles.
• Polymeric gels, on the other hand, are formed from sub-colloidal
chemical units such as branched macromolecules, where individual
particles cannot be distinguished.
• These gels are termed polymeric because their structures are
generated through the repetition of one or a few elementary units.
Chemical Bath Deposition
• Chemical Bath Deposition (CBD):
• CBD, also known as the chemical solution
method, is a solution-phase method used for the
preparation of low-cost large-area thin films from
aqueous solutions.
• Widely employed for depositing various metal
chalcogenide thin films, it involves controlled
precipitation of compounds from the solution
onto suitable substrates.
• CBD operates at room temperature without the
need for high-voltage equipment, making it
inexpensive and accessible.
• While it may suffer from reproducibility issues,
optimization of growth parameters can improve
consistency.
• The inefficiency of the CBD process in converting
precursor materials into useful deposits is a major
challenge.
Chemical Bath Deposition
• Film formation occurs through two distinct
mechanisms: growth involving atomic species at
the surface (atom-by-atom or ion-by-ion process)
and agglomeration of colloids formed in the
solution (cluster-by-cluster process).
• Both processes may interact, leading to films with
colloids included, formed by heterogeneous
nucleation on the substrate or homogeneous
nucleation in the bulk solution.
• Heterogeneous nucleation results in slow growth
of particles on the substrate, disrupted by
competing homogeneous reactions in the
solution.
• CBD offers advantages but has drawbacks,
including difficulty controlling thickness due to
changes in the growth solution over time,
depletion of reactants, and uneven bath-tosurface volume leading to waste and device
defects.
Sonochemical and Arrested
Precipitation Technique
•
Sonochemistry involves synthesizing nanoparticles using ultrasound,
leveraging the phenomenon of acoustic cavitation effects in liquids.
•
Acoustic cavitation leads to the formation of vacuum bubbles through
periodic compression and re-refraction of sound waves in the liquid,
facilitated by ultrasonic transducers.
•
These cavitation bubbles play a crucial role in nanoparticle formation.
•
Arrested precipitation is a controlled technique used to prepare nearly
monodisperse nanoparticles, involving the initial preparation of small
seed particles that act as nuclei for larger particle formation.
•
Thermodynamically, smaller particles are less stable than larger ones,
leading smaller crystallites to dissolve and recrystallize onto larger,
more stable crystallites—a process known as Ostwald ripening.
•
To prevent secondary growth, solvents like acetonitrile are used as
capping agents. For example, tri-n-octylphosphine selenide (TOPSe)
serves as a capping agent for synthesizing CdSe nanocrystalline
particles.
Photochemical Synthesis of Nanoparticles:
• This synthesis method occurs in the presence of light,
typically UV or visible light, where chemical reactions are
initiated by photons.
• Photochemical reactions often yield reduced nanoparticles
of metals such as silver (Ag), gold (Au), etc.
• For instance, in the synthesis of gold nanoparticles, an
aqueous solution of chloroauric acid produces Au^+ ions,
which are then reduced in the presence of UV light to form
metallic Au nanoparticles.
• The reduction reaction is represented
Photochemical
Method
• The color of the resulting sample, originating from surface
plasmon resonance, depends on the size of the
nanoparticles formed.
Hydrothermal
• The term "hydrothermal" originates from the Greek words
"hydrous" (water) and "thermal" (heat).
• Hydrothermal synthesis refers to heterogeneous chemical
reactions that occur in the presence of a solvent medium
at temperatures above room temperature (>25 °C) and
pressures greater than 0.1 MPa in a closed system.
• The solvent medium can be aqueous (water) or nonaqueous (alcohol), and water, due to its abundance and
unique properties, is commonly used in hydrothermal
reactions.
• Crystallization processes under hydrothermal conditions
typically occur at autogenous pressure, where the
solution reaches a specific saturated vapor pressure
corresponding to its temperature and composition.
Hydrothermal
• Hydrothermal Autoclave Characteristics:
1. Chemical Inertness: The autoclave should be resistant to acids, bases, and
oxidizing agents to prevent contamination.
2. Ease of Assembly: It should be easy to assemble and disassemble for
convenient use.
3. Temperature Gradient: Sufficient length should be provided to achieve a
desired temperature gradient within the autoclave.
4. Leak-proof Design: The autoclave should be leak-proof at the desired
temperature and pressure to ensure safety and efficacy.
5. Durability: It should withstand high pressure and temperature conditions
for extended durations without failure.
• Advantages of Hydrothermal Synthesis:
• Cost-Effectiveness: Hydrothermal methods offer cost advantages in terms
of instrumentation, energy, and precursor materials compared to many
other synthesis techniques.
• Low Reaction Temperatures: The use of low reaction temperatures avoids
issues encountered with high-temperature processes, such as poor
stoichiometric control and stress-induced defects.
Top-Down Approach
CHAPTER 8 FROM THE BOOK «Nanotechnology
Synthesis to Applications»
Edited by
Sunipa Roy, Chandan Kumar Ghosh,
and Chandan Kumar Sarkar
Physical Methods-all Milling
Ball milling, or mechanical alloying, is a lowcost process used in powdered metallurgy for
generating fine powder.
• It involves a hollow cylindrical shell filled
with steel or rubber balls, rotating about its
axis, creating high-energy impacts.
• High-energy ball milling is required for
nanoparticle synthesis, involving even
greater energy.
• During high-energy ball milling, powder
particles undergo high-energy impacts,
leading to plastic deformation and fracture.
• Chemical reactions may also be initiated due
to the high energy involved.
• The newly generated surfaces enable further
reactions and the formation of
nanoparticles.
Lithography
• Introduction to Lithography:
• Etymology: Lithography originates from the Greek words "lithos"
meaning stone and "graphein" meaning writing or drawing.
• Key Principle: Lithography involves transferring geometric patterns
from a mask onto a wafer, typically made of silicon (Si), using a
resist material.
• Application: Lithography plays a crucial role in the fabrication of
micro- and nanoelectronic devices, meeting the increasing
demand driven by Moore's law.
• Evolution: Lithography has evolved from shadow printing
techniques used in industries like printing and circuit board
patterning.
Lithography
• Advanced Lithographic Techniques:
• Recent Developments: Ion beam lithography, X-ray
lithography, electron beam lithography (EBL), and other
advanced lithographic techniques have emerged with
improved control and higher resolution.
• Advantages: These techniques offer better precision and
resolution compared to traditional photolithography
methods.
X-ray Lithography
•
Overview: X-ray lithography is a modern lithographic technique used to transfer geometric
patterns onto the surface of silicon wafers.
•
Development: First developed by International Business Machines (IBM) in 1969, achieving a
resolution of approximately 20 μm.
•
Principle: X-rays generated from synchrotron radiation are employed to create the desired
pattern.
•
Process: Similar to photolithography, a thick layer of resist is exposed to a highly intense X-ray
beam through a patterned mask. The pattern is etched into the resist substrate, producing a
negative replica of the mask pattern.
•
Mask Materials: Mask materials typically have low atomic mass to avoid X-ray attenuation.
Polymethyl methacrylate (PMMA) is a commonly used resist material.
•
Substrate: Substrate material should be conductive in nature to facilitate the lithographic
process.
•
Resolution: Resolution in X-ray lithography can be increased by decreasing the wavelength of
the X-ray.
•
Alignment Challenges: Proper alignment of the mask with the resist poses a significant challenge
due to the inability of visible light to penetrate through the X-ray membrane.
Electron Beam Lithography
•
verview: Electron beam lithography (EBL) is a technique used to write patterns
directly onto resist-coated substrates using a focused electron beam.
•
Development: Derived from scanning electron microscopy (SEM), EBL has been in use
since the early 1960s.
•
Direct Writing: EBL employs a highly focused Gaussian-shaped electron beam to
write patterns pixel by pixel on the substrate. The beam movement can be raster or
vector type.
•
System Components: EBL systems consist of electron sources, electron focusing
optics, blankers to control the electron beam, beam generators, and mechanical
systems to hold the substrate.
•
Resolution: EBL enables the fabrication of electronic devices with dimensions as small
as 10 nm without the need for projection optics or masks.
•
Lift-Off Process: An important technique in EBL, the lift-off process involves several
steps including exposure of resist, development, solvent removal, and substrate
soaking to remove remaining resist and unreacted materials.
•
Projection Printing: Another scheme in EBL involves projection printing, pioneered by
Bell Laboratories in 1989. This technique, known as SCALPEL, utilizes a membrane
mask with a patterned layer to scatter electrons selectively, creating a contrast
image on the substrate.
Ion Beam Lithography (IBL)
• Compare to other lithographic techniques, Ion Beam Lithography (IBL)
is less known but offers significant versatility and capability.
• Unlike electron beam lithography (EBL), IBL uses ions for scanning,
resulting in higher resolution (*2 nm) due to the smaller de Broglie
wavelength of ions compared to electrons.
• The working principle of IBL is similar to EBL, but with higher
resolution and no back scattering of electrons, leading to superior
resolution.
• Pixel size in IBL corresponds to the beam spot size, reducing dwell
time on each pixel.
• IBL allows for direct writing on resistless structures and can be used
for ion implantation to fabricate locally doped mask layers.
• IBL offers direct writing capabilities on resistless structures, facilitating
faster fabrication.
• Ion implantation can be utilized for locally doped mask layers,
enabling pattern generation in selective etching processes.
• In some cases, ion beams can initiate chemical reactions, expanding
the range of applications for IBL
Characterization of NPs
Chapter 4 From nanobook10
Advanced Characterization Techniques
From nanobook5
Characterization of NPs
• Nanoparticle synthesis can be achieved through various methods, each with its own advantages
and disadvantages.
• Tuning synthesis parameters allows for the preparation of nanoparticles with different sizes and
shapes.
• Surface atoms of nanoparticles significantly influence their properties, such as color and melting
point.
• For instance, the melting point of gold nanoparticles decreases from 1337 K in bulk form to 600 K
for nanoparticles with a diameter of 2 nm.
• Highly sensitive instrumentation with atomic-level resolution is necessary to characterize
nanoparticle properties, behavior, and structural dimensions accurately.
• Nanoparticle and nanomaterial characterization primarily involves microscopy and spectroscopy
methods.
• Microscopy techniques rely on imaging through radiation or particle beams.
• Spectroscopy methods measure shifts in radiation wavelength resulting from interaction with
matter.
Characterization X-Ray Diffraction
• X-ray is a valuable tool for investigating the proper phase
formation of synthesized materials.
• Crystalline materials exhibit a regular arrangement of atoms,
causing X-rays to diffract when incident upon them, similar
to the diffraction of light from gratings.
• In contrast, amorphous materials do not show crystallinity
and thus do not produce diffraction patterns, allowing X-rays
to differentiate between crystalline and amorphous
materials.
• Each material possesses its unique crystal structure with
definite lattice parameters, which can be determined using
X-ray diffraction.
X-Ray Diffraction
Scanning Electron Microscopy
• SEM is a widely used technique for characterizing the shape and
size of nanostructures, employing electrons instead of light for
imaging.
• A typical SEM setup consists of an electron gun positioned at the
top of the microscope, which emits electrons via either thermionic
emission or the electric field emission mechanism.
• Thermionic emission involves allowing current to pass through a
tungsten wire, generating electrons due to thermal energy.
Alternatively, LaB6 is used for field emission, where electrons are
liberated via tunneling in the presence of an electric field.
• Electrons emitted from the gun are formed into a beam by
electromagnetic lenses and accelerated as they pass through a
column.
• When the electron beam strikes the sample surface, it dislodges
some electrons from the sample.
• SEM operates on the principle of elastic and inelastic collisions
between the incident electrons and electrons within the sample.
Transmission electron
microscopy-TEM
• TEM is among the most advanced instruments, leveraging the
wave nature of electrons for imaging.
• A typical TEM setup is illustrated in Figure 4.11a.
• In contrast to SEM, which uses scattered electrons for imaging,
TEM operates by transmitting or penetrating electrons through
thin samples, usually less than 200 nm.
• TEM employs electrons accelerated to energies of a few hundred
keV, significantly higher than those used in SEM.
• The higher energy of the accelerated electrons in TEM is essential
to achieve wavelengths comparable to the lattice spacing of the
sample, facilitating electron diffraction.
• The working principle of TEM revolves around the diffraction of
electrons from the sample, necessitating electrons with
wavelengths on the order of the lattice spacing.
• This high energy is crucial for achieving the necessary electron
wavelength for diffraction
Scanning probe
microscopy
• SPM is based on scanning a surface using a sharp tip
with a radius of curvature typically ranging from 3 to
10 nm.
• The tip, mounted on a flexible cantilever, follows the
surface profile during scanning.
• Unlike TEM, SPM doesn't require the sample to be
sliced into thin layers, avoiding sample damage.
• The key advantage of SPM over other microscopies
like SEM or HRTEM is its ability to provide 3D imaging
of the sample surface with atomic-level resolution.
• Unlike TEM and SEM, SPM doesn't necessitate
vacuum environment conditions for operation.
Scanning Tunneling Microscopy: ST
Scanning probe microscopy
Atomic Force Microscopy:
•AFM is a powerful tool used to measure the topography of
nonconducting substrates, complementing the capabilities of STM.
•It has also been adapted for force measurement purposes.
•The basic setup of AFM includes several key components: a cantilever
with a sharp tip, a laser diode for tip deflection measurement, a mirror
for laser deflection, a feedback circuit for tip position control,
photodiodes for tip position indication, and a three-dimensional
positioning sample stage made of piezoelectric material.
•The AFM tip is fabricated using lithography techniques and typically
consists of materials like Si, SiO2, or Si3O4.
Scanning probe microscopy
Atomic Force Microscopy:
•Due to its small mass, the cantilever exhibits high flexibility and applies
minimal downward force on the sample, resulting in less distortion.
•During topographic measurements, the cantilever is pushed and pulled
back, and its deflection is proportional to the force between the tip and
the sample.
•Various methods, such as optical, piezo resistive, and tunneling current
measurement, are employed to detect cantilever deflection.
•Force spectroscopy, a technique within AFM, provides information
about local interacting forces with nanometer-scale spatial resolution.
•Unlike static AFM mode, dynamic AFM mode relies on changes in the
natural frequency, vibrating amplitude, or phase of the cantilever near
the sample surface.
Energy Dispersive X-ray Spectroscopy
• EDS is a powerful technique for analyzing the elemental
composition of a sample.
• It operates based on the principle of high-energy X-rays
ejecting 'core' electrons from atoms, leaving behind electron
holes.
• Moseley's Law correlates the frequency of released light with
the atomic number of the atom, enabling element
identification.
• The relaxation process of higher energy electrons filling the
electron holes releases energy unique to each element.
• This energy signature allows for the identification and
quantification of elements present in the sample.
How is data collected?
• EDS consists of three major parts: an emitter, a
collector, and an analyzer.
• These components are typically integrated into
electron microscopes such as SEM or TEM.
• Together, they enable the analysis of the
quantity and energy of emitted X-rays.
• EDS data is presented graphically with energy
(KeV) on the x-axis and peak intensity on the yaxis.
• Peaks on the x-axis correspond to specific
energy changes, which are converted into
corresponding atoms by a computer program.
Optical Characterization by UV-Visible Spectroscopy
• UV-Visible spectrophotometers are crucial for
determining band gaps in materials.
• The spectrophotometer consists of various
components: a light source (deuterium lamp for UV
light and halogen lamp for visible), a grating, rotating
discs, a slit, mirrors, sample and reference cells, and
a detector.
• A schematic diagram of the spectrophotometer is
shown in Fig. 14.
• Two light sources focus on the diffraction grating,
which splits light into its component wavelengths,
similar to a prism.
• The slit controls the intensity of light incident on the
rotating disc, which has three sections: a transparent
section, a mirrored section, and a black section.
Optical
Characterization
by Ellipsometer
• Powerful technique for measuring thin and ultra-thin films.
• Can measure down to <1 Å in thickness.
• Exceptionally sensitive to film thickness and uniformity.
• Suitable for investigating nearly any transparent thin film.
• Particularly useful for ultra-thin film applications (<100 nm).
Nuclear Magnetic Resonance
• Utilizes magnetic fields and electromagnetic frequencies to
study molecular structures.
• High magnetic fields are achieved using superconducting
magnets.
• Lower fields can be generated by permanent or
electromagnets.
• Samples are inserted into the magnet and positioned in the
NMR probe.
• The sample is located at the position of the strongest field
and highest homogeneity of the magnet.
• The NMR probe contains coils to excite the sample and
record signal responses at radio frequency.
Fourier Transform Infrared (FTIR)
• Utilizes Fourier transforms for analyzing
absorbed wavelengths.
• Involves shining a beam of light containing
different frequencies onto the sample.
• Measures the amount of light absorbed by the
material at various wavelengths.
• Each combination of frequencies in the light
beam is noted to obtain data points.
• The computer then analyzes these data points
in reverse to determine absorption at each
wavelength.
X-Ray Photoemission
Spectroscopy (XPS)
Also known as Electron Spectroscopy for Chemical Analysis
(ESCA).
Surface-sensitive quantitative analysis method for determining
elemental composition in solid materials.
Widely utilized for chemical characterization of thin films,
coatings, and surfaces in both industrial and research settings.
Key Advantages:
Non-destructive nature of the technique.
Wide analysis window covering all elements except hydrogen
and helium.
High sensitivity to detect elemental composition.
Exceptionally low detection limits:
For heavy metals: < 0.005% atomic concentration (ppm
by weight).
For light organic and inorganic elements: < 1%.
X-Ray Photoemission
Spectroscopy (XPS)
Principle of XPS:
When a photon strikes the sample surface, it can be absorbed
by the electronic cloud of the atoms.
High-energy photons can ionize the sample and eject
photoelectrons.
The kinetic energy of the photoelectrons is determined by the
Einstein equation, based on the electron binding energy and
photon energy.
Factors Affecting Binding Energy:
Binding energy of valence band electrons depends on elemental
composition and material characteristics like crystalline phase.
Binding energy of core electrons is specific to the atom's source
and electronic level.
Application in XPS:
XPS utilizes high-energy X-ray photons to induce photoemission
of core electrons.
The kinetic energy of the emitted photoelectrons is
characteristic of the emitting chemical element.
Dynamic Light Scattering (DLS)
DLS is a widely used technique for analyzing
particle sizes in the nanometer range.
It capitalizes on the Brownian motion of
dispersed particles in a liquid medium.
Brownian Motion Principle:
Dispersed particles move randomly due to
collisions with solvent molecules.
Energy transfer during collisions induces
particle movement, with smaller particles
exhibiting faster speeds.
Particle Size Determination:
Particle speed, influenced by factors like
temperature and viscosity, determines the
hydrodynamic diameter.
Smaller particles move faster due to more
significant energy transfer.
Dynamic Light
Scattering (DLS)
Basic DLS Setup:
Components include a laser light source, light detector, and
analysis software.
Intensity fluctuations of scattered light are analyzed to infer
particle size distribution
• Laser Scattering Setup:
• A single-frequency laser is directed towards the sample
contained in a cuvette.
• Particles in the sample scatter the incident laser light in all
directions.
• Detection and Analysis:
• Scattered light is detected at specific angles over time to
determine diffusion coefficients and particle size.
• The Stokes-Einstein equation relates diffusiaon coefficient to
particle size based on Brownian motion.
• Gray Filter Usage:
• A gray filter between the laser and cuvette attenuates the
incident laser light.
•
Filter settings are adjusted automatically or manually to
optimize signal processing.
• Multiple Detection Angles:
• Modern DLS instruments feature multiple detection angles
(e.g., 90°, 175°, and 15°).
• Choice of angle (side or back scattering) depends on sample
turbidity.
• Forward angle (15°) may be used to monitor aggregation.
Chapter 1-2-3 from the book
Chapter 4-6-7 from the book
SYNTHESIS OF NPs
Reducing
Agents in
Colloidal
Nanoparticle
Synthesis
Chemical Reduction Method to Synthesize
Noble Metal Nanoparticles
• Chemical methods enable the synthesis of
monodisperse nanoparticles or clusters with tunable
properties.
• Chemical reduction, particularly reduction of Ag+ ions
into Ag0 nanoparticles, is commonly used.
• Agglomeration of synthesized nanoparticles poses a
significant challenge in chemical reduction methods.
• Modification of techniques includes reduction
followed by stabilization.
• Various stabilizing agents, such as polyvinylpyrrolidone
(PVP) and glucose, have been examined.
• Accelerators like sodium hydroxide (NaOH) are often
added to expedite the reaction process.
Chemical Reduction Method to Synthesize
Noble Metal Nanoparticles
NP (Noble Metal)
Reducing Agent
Silver (Ag)
Borohydride (NaBH4), Citrate, Glucose,
Oleylamine, Ethylene Glycol (CH2OH-CH2OH),
Sodium Hydroxide (NaOH)
Gold (Au)
Phosphorous, Trisodium Citrate, NaBH4,
Tetraoctylammonium Bromide, Ethanol, Dodecyl
Amine, Alkane Thiol, Hydrazine, DMF (N,Ndimethylformamide)
Platinum (Pt)
NaBH4, Hydrazine, Formic Acid, H2 Gas, Alcohol,
Glycol
Polyols
• Polyols, a class of compounds, play a crucial role in the
preparation of metal nanoparticles through the polyol process.
• This process offers several advantages, including acting as a
solvent and reducing agent, resulting in well-crystallized
materials with controlled structures and morphologies.
• Polyols, such as ethylene glycol (EG), facilitate the reduction of
metal ions to zero-valent states, enabling the synthesis of metal
nanoparticles.
• The high boiling point and viscosity of polyols allow synthesis at
relatively high temperatures, preventing oxidation and
promoting controlled particle growth.
• Coordination properties of polyols minimize particle coalescence
and offer excellent colloidal stabilization, ensuring controlled
nucleation and growth of nanoparticles.
Noble Metal
Synthesis Method
Au-gold-
Polyol
Parameters
- Precursor: Gold(III) Chloride (AuCl4−), Silver(I) Ion (Ag+), Platinum(IV) Chloride (PtCl62−),
Palladium(II) Diammine (Pd(nH3)42+)
- Capping Agent: Polyvinylpyrrolidone (PVP)
- Reduction Potential (Vs. Standard Calomel Electrode, SCE)
- Ratio of PVP (Polyvinylpyrrolidone) to Au precursor
- pH of the solution
- Additional ions (e.g., Silver Nitrate (AgNO3)) for anisotropic growth
Ag-silver
Polyol
- Precursor: Silver Nitrate (AgNO3)
- Capping Agent: Polyvinylpyrrolidone (PVP)
- Ag : PVP ratio
- Additional ions (e.g., Sodium Bromide (NaBr)) for specific morphologies
- Reaction temperature
Pd-Palladium
Polyol
- Precursor: Palladium(II) Acetylacetonate (Pd(acac)2), Palladium(II) Chloride (H2PdCl4)
- Capping Agent: Oleylamine, Polyvinylpyrrolidone (PVP)
- Oxidative Power Modulator: Oxygen (O2), Iron(III) Chloride (FeCl3)
- pH of the solution
- Reaction time and duration
Pt-Platinum
Polyol
- Precursor: Hexachloroplatinic Acid (H2PtCl6)
- Capping Agent: Polyvinylpyrrolidone (PVP), Sodium Acetate
- Additives for Growth Control: Silver Nitrate (AgNO3)
- Oxidative Etching Agent: Oxygen/Chloride (O2/Cl), Iron(III) (Fe(III))
Ru-Ruthenium
Polyol
- Precursor: Ruthenium(III) Chloride (RuCl3)
- Capping Agent: Polyvinylpyrrolidone (PVP), Acetate, Sodium Hydroxide (NaOH)
- Reaction temperature
Ir-iridium
Polyol
- Precursor: Iridium(III) Chloride (IrCl3)
- Capping Agent: Polyvinylpyrrolidone (PVP), Acetate, Sodium Hydroxide (NaOH)
- Reaction temperature
- Concentration of precursor
- Boiling point of the polyol
Role of Alcohols in Colloidal
Nanoparticle Synthesis
• Green synthesis of nanoparticles is cost-effective and environmentally friendly.
• It offers advantages over conventional methods involving potentially toxic solvents and chemical reagents.
• Role of Solvent Medium:
• Selection of ecologically non-toxic solvent medium is crucial.
• The solvent medium acts as a reducing and stabilizing agent in nanoparticle synthesis.
• Control of Nanoparticle Properties:
• Nanoparticle size and shape can be controlled by adjusting the ratio of metal salt to reducing agent.
• Phase control and solvent conditions influence the structure of nanocrystallites.
• Advantages of Alcohols:
• Alcohols serve as solvent, reducing agent, and stabilizer in nanoparticle synthesis.
• Oleylamine (Oam) is a versatile alkylamine used for synthesizing various types of nanoparticles.
• Utility of Alcohols in Nanoparticle Synthesis:
• Alcohols contribute to the stability and unique properties of nanoparticles.
• They are economically appealing and less toxic compared to other solvents.
Advantages of Alcohols as Solvent
•
•
Numerous methods are available for preparing colloidal nanoparticles.
Green synthesis involves environmentally friendly reactants and solvents to minimize harm to the environment.
• Alcohol as a Green Solvent:
• Alcohol is considered a green solvent due to its abundance, biodegradability, non-toxicity, and polar nature.
• It can dissolve a wide range of organic and inorganic compounds, including transition metal catalysts.
• Role of Alcohol in Nanoparticle Synthesis:
• Alcohol serves as a reducing agent for synthesizing nanoparticles of metals like Ag, Au, Pd, and Cu.
• It plays dual roles as a reducing agent and stabilizer, leading to fine-tuned nanoparticle sizes, shapes, and surface
morphologies.
• Effect of Solvent Polarity on Nanoparticle Size:
• The polarity index of the solvent influences the size of nanoparticles synthesized.
• Gold nanoparticles synthesized in ethanol showed increased particle sizes with decreasing solvent polarity.
• Mechanistic Insights:
• Alcohol molecules align perpendicularly to nanoparticle surfaces, forming hydrogen bonds with ligand molecules
and other hydroxyl groups.
• The restructuring of solvent molecules around nanoparticles depends on the solvent's chain length and packing
ability.
Choice of Alcohol
Solvents play a crucial role in dissolving precursors and creating a
suitable environment for chemical reactions.
• While water is ideal for many reactions, non-aqueous
solvents are preferred for certain reactions due to stability
issues and incomplete solubility of non-polar compounds.
• Benefits of Non-Aqueous Solvents:
• Sol-gel approaches based on non-aqueous solvents offer
benefits such as lower dielectric constants and chelating
properties.
• Examples of Solvent-Based Nanoparticle Synthesis:
• Anderson et al. prepared ZnO nanoparticles by hydrolyzing a
zinc alkoxide precursor in different alcoholic solvents.
• Niederberger et al. developed a synthetic route for various
metal oxides using benzyl alcohol as a solvent and reductant.
• Kurawaki et al. synthesized gold nanoparticles in wateralcohol binary solutions without stabilizers, with particle size
influenced by the alcohol content.
Choice of Alcohol
•
•
Solvents play a crucial role in nanoparticle synthesis, affecting factors such as particle size, morphology, and stability.
Different solvents can lead to variations in the properties of synthesized nanoparticles.
• Colloidal Stability and Sedimentation Behavior of TiO2 Nanoparticles:
• Lee et al. investigated the stability of TiO2 nanoparticles in various solvents, observing differences in electrostatic repulsive force
and sedimentation behavior.
• 2-propanol showed superior stability, with negligible coalescence between particles compared to water, methanol, or ethanol.
• Synthesis of ZnO Nanoparticles in Different Alcohols:
• Mallick synthesized ZnO nanoparticles using ethanol, propanol, and ethylene glycol, observing variations in crystallite sizes and
stress levels.
• Different alcohols resulted in distinct particle morphologies, affecting crystalline structure and surface area.
• Effect of Solvents on ZnO Nanoparticle Synthesis via Solvothermal Method:
• Saric et al. studied ZnO nanoparticle synthesis using various alcoholic solvents, observing differences in particle morphology and
size.
• The choice of solvent influenced crystal growth and binding interactions during nucleation.
• Influence of Solvents on TiO2 Nanoparticles Synthesized by Sol-Gel Method:
• Bahar et al. synthesized TiO2 nanoparticles in alcoholic solvents, with ethanol leading to larger particle sizes due to better reaction
with precursors.
• Different processing methods, such as calcination and microwave exposure, further affected particle size and crystallinity.
Redox Potential on Polymer Nanoparticles
Polymers, consisting of repeating
monomeric units, form
nanoparticles with globular
conformation in suitable solvents,
offering diverse applications from
nanomedicine to electronics.
Investigations have elucidated the
doping mechanism, where
halogenation induces conductivity
by transforming neutral polymer
chains into polymeric cations,
facilitating charge movement under
an electric field.
Reduction of the energy gap
between valence and conduction
bands influences the material's
redox potentials, affecting its
conductivity.
Introduction of heteroaromatic
rings enables the design of
undoped polymers with inherent
semiconducting properties, offering
avenues for fine-tuning electronic
characteristics.
Advancements in conducting
polymers have facilitated the tuning
of redox potential and bandgap,
leading to applications such as
antistatic coatings, organic lightemitting panels, photovoltaic
devices, and bioelectronics.
Structural modifications in
monomers, exemplified by
polyphenylvinylene (PPV) polymers,
alter the electrochemical
properties, enhancing
processability and expanding
application possibilities.
Industrial Polymer Use
Conducting polymers are widely
researched due to their
scientific and industrial
importance.
They are extensively used in
nanoparticle synthesis,
facilitating efficient reduction
processes.
Examples include the synthesis
of silver (Ag) nanoparticles
using polyaniline (PANI) colloids
and gold (Au) nanoparticles
using poly(propylene imine)
(PPI) dendrimers.
Biopolymers like carboxymethyl
cellulose (CMC) are also utilized
for nanoparticle synthesis,
offering biodegradable
nanomaterials for biomedical
applications.
These polymeric nanoparticles
exhibit conducting properties
and redox potentials, enabling
diverse applications in
microelectronics, solar panels,
electrode batteries, etc.
The industry revolving around
conducting polymers exceeds
$200 million annually,
underscoring their significance
in various sectors.
Note: Parameters are listed with their respective synthesis methods, highlighting the differentiating factors among various nanostructure synthesis techniques.
Synthesis Method
Template-Based Methods
Differentiating Parameters
Type of template (e.g., AAO, polycarbonate, DNA,
surfactants)
Template removal technique (e.g., chemical etching,
calcination)
Soft Template-Based Methods
Type of soft template (e.g., PEO-b-PMAA–SDS complex
micelles, DNA)
Reducing and capping agents (e.g., ascorbic acid,
oleylamine)
pH and concentration of precursor materials
Surfactant-Mediated Methods
Type of surfactant (e.g., CTAB, SDS, oleic acid)
pH and concentration of precursor materials
Hydrothermal Technique
Temperature and pressure conditions
Type and concentration of precursor materials
Reaction time and duration
GREEN SYNTHESIS-Nanoparticle Synthesis via
Biological Way
Organisms have evolved mechanisms to survive in environments with high metal concentrations.
Their ability to alter the chemical composition of metals can reduce toxicity or render them harmless.
Biogenic Metallic Nanoparticles Production:
Two main classifications:
Bio-reduction: Chemical reduction of metal ions by biological methods.
Bio-sorption: Metal ions bond with organisms, forming nano-particulate structures.
Bio-reduction Process:
Dissimilatory metal reduction leads to the formation of stable metal ions.
Enzymatic oxidation results in the production of metallic nanoparticles.
Example: Metal ions reduced to harmless nanoparticles in polluted samples.
Bio-sorption Process:
Metal ions bond with peptides or cell walls of organisms.
Peptides form constant nano-particulate structures.
Metal ions must be present within the cell for these processes to occur.
Selection of Organisms:
Limited variety of organisms due to their resistance to specific metals.
Microbial resources utilized for metal salt and metal nanoparticle production:
Bacteria, fungi, algae, yeast, viruses.
Commonly Researched Metal Salts and Nanoparticles:
Silver, copper, cadmium, gold, platinum, cadmium sulfide, palladium, zinc oxide, titanium dioxide.
Biological Materials (Plant and Leaf Extracts) –
Nanoparticle Phytosynthesis
• Introduction:
• Phytosynthesis utilizes plant extracts for nanoparticle synthesis, offering a sustainable approach.
• Bio Extract Composition:
• Plant extracts contain diverse biomolecules: polyphenols, flavonoids, enzymes, etc., which play various roles in
nanoparticle synthesis.
• Mechanism:
• Interaction between leaf extract biomolecules and precursor materials leads to redox reactions, resulting in stable
nanoparticle formation.
• Control over Properties:
• Phytosynthesis allows control over nanoparticle properties such as size, shape, and functionalization, leveraging the
diverse properties of plants.
• Advantages:
• Cost-effective and eco-friendly method utilizing biomass wastes.
• Simplified isolation process without complex workup.
• Considerations:
• Extraction conditions (solvent, temperature, pH) influence nanoparticle properties and must be carefully controlled.
NPs Synthesis by reduction with plant extract
Phytosorption involves substances from plant extracts attaching to nanoparticle
surfaces, improving their properties and enabling new applications.
Role of Attached Substances:
Molecules present on the nanoparticle's surface from plant extracts impart novel
properties, expanding potential applications.
Example: Green Synthesis of Silver Nanoparticles with Eugenol:
Eugenol, a phenylpropanoid compound found in plants, acts as a reducing agent.
Known for anti-inflammatory, antibacterial, antifungal, and antioxidant properties.
Silver nanoparticles synthesized with eugenol exhibit enhanced antibacterial effects
compared to those from traditional methods.
Variability in Copper Nanoparticles:
Copper nanoparticles synthesized with leaf extracts offer diverse possibilities.
Final properties influenced by fixed biomolecules and synthesis treatment geometry.
Miscellaneous Reductants
for NPs Synthesis
•
•
Microorganisms: Promising tools for nanoparticle synthesis.
Bacteria, algae, fungi, and yeast are typical living organisms used in the
last decade for their redox enzyme or electron-donating molecules
facilitating nanoparticle bioprocesses.
•
Role of Living Cells in Nanoparticle Synthesis:
•
Living cells are increasingly used due to their potential for genetic
modification.
•
Bacteria, fungi, and algae typically employ two methods for reducing
ions: intracellular reductase enzymes or extracellular carbonyl groups.
•
Mechanisms of Nanoparticle Formation by Cells:
•
Active internalization of ions into cells through ionic channels.
•
Accumulation of ions in the cytosol facilitated by stabilizing agents.
•
Fixing and reduction of ionic species by proteins with carboxylic groups in
the cell wall/membrane.
•
Reduction of ions leading to the formation of clusters during the
nucleation process and eventual nanoparticle formation.
•
Microorganisms offer various mechanisms for metallic nanoparticle
formation.
•
Ongoing research in this field holds promise for various applications.
•
•
•
Miscellaneous Reductants for NPs SynthesisUse of Bacteria
Prokaryotes, particularly bacteria, have been increasingly used for metallic nanoparticle
synthesis in the past decade.
Bacteria offer advantages such as abundance, adaptability to extreme conditions, fast
growth, and easy manipulation.
Studies:
•
Gold Nanoparticles with Rhodopseudomonas capsulata:
• He et al. utilized the photosynthetic bacteria Rhodopseudomonas capsulata to
produce extracellular gold nanoparticles.
• Nicotinamide adenine dinucleotide hydride (NADH)-dependent reductase enzyme
played a key role in reducing gold ions to nanoparticles.
• pH variation in the growth medium influenced the shape and morphology of
nanoparticles.
•
Gold Nanoparticles with Delftia acidovorans:
• Johnston et al. used the gram-negative aerobic bacteria Delftia acidovorans to
produce gold nanoparticles.
• The bacteria excrete peptide delftibactin, acting as the reducing and stabilizing
agent for nanoparticle generation.
•
Silver Nanoparticles with Bacillus licheniformis:
• Kailashwaralal et al. synthesized stable silver nanoparticles using the nonpathogenic
bacteria Bacillus licheniformis.
• Nanosilver was produced by bioreduction of aqueous silver cations using culture
supernatant of Bacillus licheniformis.
•
Bacteria offer a promising avenue for the biological synthesis of metallic nanoparticles.
•
Understanding bacterial mechanisms can lead to controlled synthesis processes with
varied properties.
•
Palladium Nanoparticles:
•
Palladium nanoparticles are utilized as catalysts in
dehalogenation and hydrogenation reactions.
•
Schlüter et al. (2014) demonstrated the synthesis of
palladium nanoparticles using bacterial species from
heavy metal-contaminated alpine sites.
•
Pseudomonas cells were identified as producers of
catalytically active palladium nanoparticles, particularly
useful in reductive dehalogenation reactions.
•
Silver Nanoparticles:
•
Saifuddin et al. (2009) developed a novel synthetic
method for silver nanoparticles using a combination of
Bacillus subtilis culture filtrate and simultaneous
microwave irradiation in an aqueous medium.
•
Shahverdi et al. (2007) achieved rapid synthesis of
nanosilver by introducing culture supernatants of E. coli,
Enterobacter cloacae, and Klebsiella pneumonia to a
solution of silver salt.
•
Lactobacillus strains exposed to metal ions biosynthesize
nanoparticles within bacterial cells, as demonstrated by
Nair et al. (2002) and Korbekandi et al. (2012).
•
Other Metal Nanoparticles:
•
Bacillus species exhibit excellent metal bioaccumulation
capacities, as reported by Kalimuthu et al. (2008) and
Pugazhenthiran et al. (2009).
•
Pollmann et al. (2006) explored Bacillus sphaericus'
ability to accumulate toxic metals such as lead, cadmium,
copper, and uranium, attributed to proteins on the
bacterial cell surface.
Future Prospects
Challenges:
• Microbial synthesis of metallic nanoparticles (MNPs) is laborintensive and lacks control over size and shape, leading to nonmonodispersed products (Shende et al., 2022).
• Precise mechanisms of MNPs synthesis are not fully understood,
necessitating thorough research to elucidate the process.
Important Considerations:
• Bacterial strains should be selected based on growth rate,
biochemical profiles, and enzyme activities.
• Growth parameters such as media, pH, and temperature must be
optimized for maximal metabolite secretion and enzyme activity.
• Process parameters like metabolite concentration, time, and
temperature need standardization and optimization for efficient
MNPs synthesis.
• Downstream processes for extraction and purification should be
environmentally friendly, energy-efficient, and cost-effective.
• MNPs synthesized via bio-based approaches exhibit stability and
improved bio-catalytic activities.
Miscellaneous Reductants for NPs SynthesisUse of Fungi
Advantages of Fungi:
• Fungi offer advantages over bacteria for the production of metal
nanostructures.
• Fungal mycelia have a large surface area, facilitating rapid downstream
processing of bioreduction reactions.
• Fungal synthesis can result in stable nanoparticles with no flocculation,
attributed to enzymatic activity.
Research Findings:
• Mukherjee et al. (2001) demonstrated the preparation of extracellular silver
nanoparticles using Fusarium oxysporum, noting long-term stability without
particle flocculation.
• Ahmad et al. (2003) attributed the reduction of silver cations and nanoparticle
stability to the enzymatic activity of NADH-dependent reductase.
• Fungal cells secrete higher amounts of protein compared to bacteria,
potentially amplifying nanoparticle production.
Case Study:
• Vahabi et al. (2011) tested Trichoderma reesei for extracellular silver
nanoparticle synthesis, observing sizes ranging from 5 to 50 nm.
• T. reesei can produce high quantities of enzymes, up to 100 g/L, leading to
substantial nanoparticle yields.
Intracellular Synthesis of Nanoparticles
• Advantages of Intracellular Synthesis:
•
•
While extracellular synthesis offers simplicity and low cost, intracellular synthesis procedures are vital for specific
environmental applications.
Sanghi et al. (2009) utilized the white rot fungus, Coriolus versicolor, for generating and accumulating intracellular silver
nanoparticles, offering a potential solution for the reduction and removal of unintended metal ions from water samples.
• Exploration of Magnetic Nanoparticles:
•
Magnetic nanoparticles have been reported to be produced by endophytic fungus Verticillium sp. and pathogenic fungus F.
oxysporum (Sun et al., 2002; Bharde et al., 2006), with applications in magnetic resonance imaging, magnetic recording, and
position sensing.
• Consideration of Safety:
•
While fungi have advantages, safety concerns arise, especially with pathogenic strains. However, nonpathogenic fungi like
Trichoderma asperellum and Trichoderma reesei, which produce Ag nanoparticles, offer safer alternatives for commercial
use in various industries.
• Efficient Synthesis by Microorganisms:
•
•
Kaul et al. (2012) synthesized iron nanoparticles from ferric oxide solution using bacteria and fungi. Among these
microorganisms, C. globosum proved most efficient for iron nanoparticle synthesis.
They also demonstrated the synthesis of magnesium nanoparticles from magnesium salts using fungal species, with A.
fumigatus producing Mg nanoparticles extracellularly and P. chlamydosporium producing them intracellularly in response to
different metal salts.
• Biosynthesis of Metal Nanoparticles by Aspergillus Species
• Study by Raliya and Tarafdar (2014):
• Raliya and Tarafdar reported the biosynthesis of
magnesium, zinc, and titanium nanoparticles using various
Aspergillus species.
• The study utilized soil-borne Aspergillus strains, including
A. fumigatus, A. niger, A. tubingensis, A. oryzae, A. flavus,
and A. terreus, collected from arid agricultural lands in
Rajasthan, India.
• Experimental Procedure:
• The isolated fungal strains were authenticated and
cultured to obtain cell-free culture filtrate.
• This filtrate was then added to different metallic precursor
compounds to synthesize nanoparticles.
• Results:
• The study yielded nanoparticles of varying sizes, indicating
the versatility of the fungal strains in nanoparticle
synthesis.
• Extracellular enzymes secreted by the fungal cells likely
acted as reducing and surface-stabilizing agents, facilitating
nanoparticle production.
Fungal Isolates Used in Nanoparticle Production
• Fungi play a significant role in nanoparticle synthesis, offering
advantages over other methods.
• Understanding the fungal isolates used in nanoparticle
production is crucial for exploring their applications.
• Fungal Isolates:
• Examples of commonly used fungal isolates include:
• Aspergillus niger: Soil-derived isolate known for
synthesizing silver and gold nanoparticles.
• Fusarium oxysporum: Plant pathogen capable of producing
silver and copper nanoparticles.
• Trichoderma viride: Soil fungus associated with the
synthesis of silver nanoparticles.
• Candida albicans: Yeast species known for its role in silver
nanoparticle synthesis.
• Applications of Nanoparticles:
• Nanoparticles synthesized by fungi find diverse applications:
• Medical and therapeutic uses.
• Optoelectronics and related technologies.
Miscellaneous Reductants for NPs SynthesisYeast
• Yeasts are unicellular fungi widely used in
various industries due to their easy handling in
laboratory conditions.
• Saccharomyces cerevisiae is the most common
yeast species, utilized in fermentation
processes for producing alcohol and carbon
dioxide.
•Role of Yeast in Nanoparticle Synthesis:
• Yeasts can utilize oxygen from different
sources for growth, which can be exploited for
metallic nanoparticle synthesis through
reduction processes.
• Dead yeast material can also serve as a
reducing agent by absorbing metallic ions and
undergoing reduction, although the exact
mechanism is not fully understood.
•Nanoparticles Synthesized by Yeasts:
• Yeasts have been utilized to synthesize
nanoparticles of various metals, including gold,
cadmium sulfide, silver, lead sulfide, selenium,
ferrous oxide, and antimony.
Miscellaneous Reductants for NPs
Synthesis-Use of Algae
•
•
Algae represent a less explored but promising area for
nanoparticle synthesis.
A small number of reports exist on the use of algae for
preparing metal nanoparticles.
• Examples of Algal Platforms for Nanoparticle Synthesis:
• Singaravelu et al. utilized Sargassum wightii to produce
extracellular and highly stable gold nanoparticles, achieving
95% production within 12 hours of incubation.
•
Chakraborty et al. described the use of various algal species,
including Cladophora prolifera, Lyngbya majuscule, Spirulina
subsalsa, and others, for the formation and accumulation of
gold nanoparticles.
• Recent Advances:
• Aziz et al. utilized freshwater green algae Chlorella
pyrenoidosa for biosynthesis of silver nanoparticles with a
particle size distribution between 5 and 15 nm.
• Govindaraju et al. observed extracellular formation of
spherical silver nanoparticles (7–16 nm) when the biomass of
edible cyanobacteria Spirulina platensis was exposed to
aqueous AgNO3.
Amino Acids and Peptides in Colloidal
Nanoparticle Synthesis
• Colloidal nanoparticles are soft materials with
widespread applications in various fields such as
material science, chemistry, biology, medicine,
and industry.
• Fabricating colloidal nanoparticles of metals,
metal oxides, and semiconductors with diverse
properties is crucial for their use in sensors,
medicines, and catalysts.
• Scientists from different disciplines are interested
in understanding the structure and function of
these nanoparticles.
• Colloidal nanoparticles may exhibit significant
optoelectronic properties, making them
promising for optical probes due to their color
changes based on shape and size variations.
Chapter 8 from nanobook6
Tyrosine as Reducing Agent
• Tyrosine is a non-essential amino acid with a polar side group.
• In 2004, Sastry and colleagues demonstrated that under alkaline
conditions, tyrosine acts as an excellent reducing agent for metal
ions.
• They used tyrosine to reduce Ag+ ions and synthesize silver
nanoparticles in an aqueous medium.
• The reduction process occurs through ionization of the phenolic
group in tyrosine to tyrosinate, capable of reducing Ag+ ions and
converting to a semi-quinone structure.
• The resulting colloidal silver nanoparticles, reduced by tyrosine, can
be separated as a powder-like material that is easily redispersible in
water.
Tyrosine as Reducing Agent
• Sastry and colleagues demonstrated the use of
tyrosine-capped gold nanoparticles to reduce
silver ions under alkaline conditions.
• This pH-dependent reducing capability of tyrosine
molecules leads to the formation of gold core–
silver shell bimetallic colloidal conjugate
nanoparticles.
• By capping gold nanoparticles with tyrosine, the
reducing agent is bound to the surface of the gold
nanoparticles, enabling selective reduction of
silver ions only on the gold surface.
• This approach avoids the nucleation and growth
of colloidal silver nanoparticles in solution.
Tryptophan as Reducing Agent
• Tryptophan, an essential amino acid with an
indole side chain, is utilized by Iosin and
colleagues as a reducing and stabilizing agent
for colloidal gold nanoparticles.
• They reported a rapid synthesis of colloidal
gold nanoparticles using tryptophan.
• The synthesis process's kinetics and crystal
growth are significantly influenced by
temperature, with higher temperatures
favoring the formation of anisotropic
nanoparticles such as triangles and hexagons.
Tryptophan as
Reducing Agent
• In 2019, we utilized urea-modified tryptophan as an in situ
reducing and stabilizing agent for fabricating gold nanoparticles.
• These gold nanoparticles served as Suzuki–Miyaura crosscoupling catalysts in water.
• Previous reports indicate that tryptophan's electron-donating
functionality enables in situ gold nanoparticle synthesis.
• By modifying the redox-active tryptophan residue with urea, we
aimed to develop a method for in situ gold nanoparticle
synthesis in water.
• Urea-modified tryptophan (1 mg) was dissolved in 5 ml water,
and HauCl4 solution (20 mg in 2 ml water) was added, resulting
in a colorless solution.
• The colorless solution turned violet after five minutes, indicating
the formation of gold nanoparticles (Au0) in aqueous media.
Tryptophan as
Reducing Agent
• The synthesis of gold nanoparticles using ureamodified tryptophan was characterized by UV-Vis
spectroscopy.
• The UV-Vis spectrum of the urea-modified
tryptophan–gold nanoparticle solution exhibits a
characteristic band at 545 nm, indicative of colloidal
gold nanoparticles with a size range of 15 nm (at a
tryptophan : HauCl4 ratio of 10 : 1).
• These colloidal gold nanoparticles remain stable at
room temperature for approximately three months
without any deposition.
• Varying the ratio of HauCl4 and urea-modified
tryptophan results in the formation of gold
nanoparticles of various sizes, as confirmed by UVVis spectra.
Tyrosine-containing Small Peptides as
Reducing Agent
• n 2005, a method for synthesizing colloidal gold
nanoparticles was reported.
• Peptide in situ reduction technique was employed at
ambient temperature, using a specially designed
tripeptide.
• The peptide contained a C-terminus tyrosine residue,
which facilitated the reduction of Au^3+ to Au^0,
resulting in highly stable Au colloids.
• The tripeptide was synthesized conventionally,
followed by removal of the Boc-group to obtain the
reducing agent NH2-Leu(1)-Aib(2)-Tyr-OMe.
Tryptophan-containing Small Peptides as
Reducing Agent
• The synthesis of colloidal gold and silver nanoparticles using small
peptides with a tryptophan residue at the C-terminus was explored by
Si and Mandal. They conducted the synthesis at pH 11 and attributed
the reduction of metal ions to the tryptophan residue, potentially
through electron transfer. Spectroscopic techniques such as UV-Vis
and fluorescence spectroscopy were employed to examine the
reductive properties of tryptophan. The resulting
peptide-functionalized colloidal metal nanoparticles were
characterized using various analytical methods including UV-Vis
spectroscopy, TEM, FT-IR, and thermogravimetric analysis.
Amino Acids as Stabilizing Agent for Colloidal
Nanoparticles
• Cysteine, a semi-essential amino acid, contains a thiol side chain that acts as a
nucleophile in enzymatic reactions.
• Lee et al. discovered that both l-cysteine and d-cysteine play a role in directing the
synthesis of chiral plasmonic gold nanoparticles.
• The chiral components present in the amino acids and on the surface of the gold
nanoparticles facilitate enantioselective interactions, leading to the development of
highly twisted chiral helicoid morphologies.
• Marinescu et al. introduced a novel synthesis route for magnetite nanoparticles using
l-aspartic acid or l-glutamic acid, resulting in colloidal nanomagnetites characterized
by various techniques.
• Zare et al. synthesized gold nanoparticles employing polyfunctional amino acids such
as l-arginine and l-aspartic acid, with sodium citrate reducing the gold salt to form
stable nanoparticles.
• Sadhu et al. demonstrated a one-pot seed-mediated synthetic method for au–FexOy
nanocomposites, utilizing l-tryptophan as a stabilizing agent and Fe powder as the
reductant.
Peptide Matrix as Stabilizing Agent for
Nanoparticles
• Organic/inorganic hybrid materials are gaining significant attention due to their diverse
applications in various fields such as light-emitting materials, photovoltaics, non-linear optics,
sensors, energy storage, and biological sciences.
• These hybrid materials combine the advantageous properties of both organic and inorganic
components, allowing for tailored functionalities.
• One promising class of hybrid materials involves composites of supramolecular organic matrices
and inorganic semiconducting colloidal nanoparticles or quantum dots.
• Quantum dots are nanocrystals with critical dimensions smaller than the Bohr radius of the
material, offering unique electronic properties.
• CdS colloidal nanocrystals, for example, have been extensively studied in composites with
polymeric materials, but they often exhibit low quantum yields due to surface defects.
• To address this issue, supramolecular organic capping agents are used to reduce defects and
enhance the photoluminescence efficiency of quantum dots.
• In 2012, a study reported the synthesis of CdS nanoparticles stabilized by a peptide matrix.
• The peptide, boc-Gly-aib-Gly-OMe, formed a crystal with distorted β-turn conformations,
interlinked through intermolecular hydrogen bonds.
• These peptide units further self-assembled into supramolecular monolayer sheet-like structures,
stabilizing the CdS nanoparticles.
Nanomaterials Biosynthesized by Plants
•
Plants possess remarkable bio-reduction capabilities, acting as chemical factories to produce
a diverse range of nanomaterials.
•
This ability stems from the abundance of naturally occurring substances present in various
parts of plants, including tannins, proteins, alkaloids, flavones, polyphenols, flavonoids,
terpenoids, and saponins.
•
Secondary metabolites found in plant extracts serve as reducing, stabilizing, and capping
agents in bio-reduction reactions for nanomaterial synthesis.
•
Polyphenols, known for their antioxidant properties, have a significant impact on the
reduction and protection abilities in nanomaterial synthesis.
•
These substances shield plants from free radicals generated during photosynthesis and
interaction with external sources.
•
Plants can be utilized for the synthesis of metal precursors to nanomaterials through
intracellular, extracellular, or phyto-constituents pathways, whether they are in active or
dormant states.
•
Typically, plant parts are rinsed with distilled water, boiled, and then the extract solution is
purified and mixed with metal solutions to produce nanoparticles.
•
The successful formation of nanoparticles is often indicated by a change in the color of the
solution.
•
Plant extracts have been employed in the synthesis of various nanoparticles, including cobalt,
palladium, gold, copper, silver, zinc oxide, and platinum nanoparticles.
Nanomaterials Biosynthesized
by Plants
Mechanism of Plant-Mediated Nanomaterial
Production
• Nanomaterial production using plants as
catalysts typically involves three main
stages: reduction, growth, and termination.
• During the reduction phase, electrons from
phytoactive substances are transferred
from metallic ions to metal atoms, resulting
in the formation of metal nanoparticles.
Nanomaterials
Biosynthesized by Plants
Mechanism of Plant-Mediated
Nanomaterial Production
• These metal nanoparticles exhibit various geometries,
including linear, rod-like, triangular, hexagonal, and cubic
shapes.
• The growth phase involves the continued development and
aggregation of nanoparticles, leading to the formation of
larger structures.
• Finally, in the termination phase, phytoactive components
with antioxidant characteristics surround the nanomaterials
to maintain their stability.
Polysaccharides
• Polysaccharides are biopolymers composed of
saccharide units linked by glycosidic bonds, primarily
hexose units.
• Their hierarchical supramolecular structure,
featuring intra- and intermolecular hydrogen bonds,
gives rise to linear, branched, and complex
configurations.
• Morphologically, polysaccharides like starch and
cellulose exhibit a combination of highly ordered
crystalline regions and less ordered amorphous
regions.
• Hydrolysis of the amorphous regions yields highly
sustainable crystalline nanomaterials, such as
nanocellulose, on a large scale.
• Polysaccharide nanomaterials, including
nanocellulose, are integral in synthesizing colloidal
nanoparticles and find applications in various fields
like sensors, solar cells, and drug delivery systems.
Polysaccharides
• Surface modification of polysaccharides through processes like
etherification, esterification, and oxidation enhances their capacity for
colloidal nanoparticle synthesis.
• Modified polysaccharides often exhibit improved performance, particularly
in size, shape, and uniformity control of colloidal nanoparticles.
• Combining polysaccharides with colloidal nanoparticles often results in
synergistic interactions, making them suitable for applications like cancer
treatment.
• Commercial colloidal nanoparticles synthesized using polysaccharides,
whether native or modified, closely resemble those produced through
other methods, suggesting the effectiveness of polysaccharides as reducing
agents.
Polysaccharides
Starch
• Starch is widely utilized in colloidal nanoparticle synthesis due to its abundance and effective reducing
capacity.
• Structurally, starch comprises amylose (linear chains) and amylopectin (branched chains) linked by α1,4 and α-1,6 glycosidic bonds, with the composition varying based on its source.
• Starch's reducing capacity depends on reaction conditions; under mild conditions (<100°C), surface
hydroxyl groups act as reducing sites, while higher temperatures and pressures lead to increased
hydrolysis, generating stronger reducing agents.
• pH variations also impact starch's reducing capacity, with higher pH causing starch granule expansion
and exposing more reducing sites.
• Partial oxidation of starch can introduce aldehyde functional groups with enhanced reducing strength
compared to hydroxyl groups.
• Additional chemical modifications, like grafting other polymers onto starch, further enhance its
reducing capacity by introducing new reducing sites.
• These various reaction conditions and modifications contribute to starch's versatility in colloidal
nanoparticle synthesis.
Polysaccharides
Chitosan
• Chitosan, derived from chitin found in crustacean exoskeletons, is another crucial polysaccharide utilized in colloidal
nanoparticle synthesis.
• Structurally, chitin comprises N-acetyl-D-glucosamine units linked by β-1,4-glycosidic bonds, with chitosan formed through
partial deacetylation, resulting in randomly distributed d-glucosamine units within the polymer chains.
• The degree of deacetylation determines the d-glucosamine content, with higher deacetylation leading to increased dglucosamine concentration.
• The presence of d-glucosamine enhances chitosan's solubility in polar solvents and facilitates structural modification.
• Chitosan is a polycationic polymer known for its chelating ability, with a pH-dependent surface charge; at low pH, its amino
groups become protonated, resulting in a positive charge, while at high pH, its hydroxyl groups become deprotonated,
leading to a negative charge.
•
Nanotechnology in Agriculture
and Environmental Science
FIELD APPLICATION OF NPs FOR SUSTAINABLE
AGRICULTURE
•
Conventional agriculture's impact on the ecosystem
•
Overuse of fertilizers and pesticides
•
Adverse effects on the environment
•
Importance of using minimal agro-chemicals
•
Protection of the ecosystem and environment
•
Shift towards sustainable agriculture
•
Aim for higher returns with low input
•
Role of nanotechnology in sustainable agriculture
•
Enhanced efficacy
•
Utilization of nano-plant growth promoters
• Nanofertilizers
• Nanopesticides
• Nanoherbicides
•
Cost-effective applications in agriculture
•
Concerns about nanomaterials in agriculture
•
Mechanism of penetration to applied surfaces
•
Associated risks
FIELD APPLICATION OF NPs FOR SUSTAINABLE AGRICULTURE
NPs AND CROP PROTECTION
•
Food security in the context of limited resources and climate change
•
Changing climatic baselines
• Ecological pollution
• Water scarcity
• Cold, alkalinity, salinity, and toxicity of metals
•
Role of advanced nanomaterial engineering in crop production
•
Enhancement of crop production in adverse environments
•
Specific examples of nano-SiO2 and Foilar spray of FeSO4
improving plant characteristics under salinity stress
•
Acceleration of plant growth and productivity through
nanofertilizers application
•
Nanomaterials in detoxification and remediation of heavy metals
•
Improvement of rice's Cd stress tolerance through nano-Si
application
•
Reduction of abiotic and biotic stress risks through
nanomaterials
•
Control of various plant- and soil-borne diseases using
nanomaterial oxides such as CuO, Mgo, and ZnO
NANO-INSECTICIDES
FIELD APPLICATION OF NPs FOR SUSTAINABLE
AGRICULTURE
NANOFUNGICIDE
•
Impact of plant pathogens
•
•
•
•
Challenges with conventional plant pathogen control methods
•
•
•
Nonbiodegradability and impact on human and animal health
Need for nanomaterials-based antifungal alternatives
•
•
•
Cost-ineffectiveness and environmental unfriendliness
Global fungicide market size, estimated fungicide usage, and associated
harm
Harmful effects of pesticides
•
•
Phythophora, Rhizoctonia solani, Fusarium spp., and B. cinerea
Attack on soil-buried, aerial, fruit, and green tissue of plants
Significant damage to plants
Unique qualities of nanofungicides due to their small size
Development and wide variety of nanopesticide formulations
Potential benefits of nanotechnology-based products
•
•
•
Broad-spectrum use
Nontargeted effect
Addressing public concern
NANOMATERIAL AS NANOHERBICIDES
•
Utilization of nanotechnological potential for effective herbicide
delivery.
•
Nanosized preparation for improved efficacy, increased solubility, and
reduced toxicity compared to conventional herbicides
NANOMATERIAL AS NANOFERTILIZER
• Definition and purpose:
•
Nanofertilizers: Conventional fertilizers encapsulated with nanomaterials for slow nutrient release, enhancing soil fertility
and productivity [1]
• Environmental impact:
•
Slow release of nanomaterials minimizes environmental impact while maintaining high productivity [1]
• Benefits and applications:
•
•
Interaction of highly reactive nanomaterials with fertilizers enhances nutrient absorption by plants
Slow release enhances nutrient usage, bioavailability, prevents leaching, reduces volatilization, and lessens environmental
threats [1]
• Encapsulation methods:
•
Nanofertilizers can be encapsulated by entrapping with nanomaterials, coating with nanomaterials, or delivery in the form
of nanoemulsion [1]
• Factors influencing effectiveness:
•
Effectiveness depends on the preparation of nanoformulation, soil conditions, and mode of application [1]
• Agricultural impact:
•
Agricultural growth and economic distribution are influenced by fertilizer efficacy, affected by factors such as plant uptake
efficiency, leaching, soil combination, and chemical composition [1]
PLANT UPTAKE AND TRANSLOCATION OF
NANOPARTICLES
•
Bioavailability and toxicity transformation:
•
•
•
•
•
Absorption process:
•
Plant roots absorb NPs, leading to accumulation in subcellular and cellular organelles
•
Bioaccumulation as the first step of NPs absorption [1]
Movement and internalization:
•
NPs travel apoplastically across extracellular gaps until reaching the vascular cylinder, where they
ascend unidirectionally through the xylem
•
For symplastic movement, NPs enter the vascular cylinder by crossing the Casparian strip barrier
through binding to endodermal carrier proteins and travel through plasmodesmata via
cytoplasmic internalization [1]
Impact of NPs:
•
NPs unable to internalize aggregate on casparian strips, modifying their absorption
•
NPs taken up by cells are found in nuclei, cortical cytoplasm, and cell walls of the epidermis [1]
Factors influencing NPs accumulation and translocation:
•
•
Transformations required to increase bioavailability and decrease toxicity of NPs [1]
Physiological structure of cells, interaction of soil with nanomaterials, and intrinsic stability of
nanoparticles [1]
Influence of NP coating and morphology:
•
NP coating and morphology significantly influence their action on plants [1]
FOLIAR AND SOIL EXPOSURE OF NFs IN PLANTS
•
Nanobioscience holds immense potential in revolutionizing
fertilizer technology for global agriculture.
•
Nanofertilizers (NFs) represent a breakthrough in enhancing
food production capabilities worldwide.
•
NFs are essentially nutrients encapsulated or coated by
nanoparticles, allowing for precise delivery and utilization by
plants.
•
They can be synthesized using either synthetic chemicals or
through green methods utilizing plants, fungi, or bacteria.
•
Green synthesis of NFs is environmentally friendly, utilizing
bio-organisms and minimizing the use of toxic substances or
chemicals.
•
NFs play a crucial role in improving soil fertility, nutrient
bioavailability, and ultimately, crop yield and quality.
•
Their unique properties, including vast surface area and
controlled nutrient release, make them ideal for advanced
agriculture practices.
FOLIAR AND SOIL EXPOSURE OF NFs IN
PLANTS
• Nanoparticles (NPs) encounter the cuticular barrier upon foliar application,
necessitating passage through specific pathways to reach plant tissues.
• The cuticle layer of leaves, characterized by a waxy coating, comprises the
cuticular and stomatal pathways, each serving distinct roles.
• Nonpolar solutes navigate the lipophilic pathway, entering plant leaves through
diffusion processes.
• Conversely, polar solutes utilize the stomatal pathway for entry into plant tissues.
• NPs smaller than 5.0 nm can penetrate the cuticle via the cuticular route, while
larger NPs have shown limited entry through foliar application in certain studies.
• Variations in leaf ultrastructure, stomatal characteristics, and size across plant
species may influence NP uptake via foliar application.
• Once inside the leaf apoplast, NPs may traverse long distances through the
plant's circulatory system.
FOLIAR AND SOIL EXPOSURE OF NFs IN
PLANTS
• Factors influencing uptake:
• Plant morphology, growth stage, exposure conditions, particle size, and rhizosphere
processes influence the uptake of NPs by the roots [1]
• Influence of particle characteristics:
• NPs with specific characteristics, such as surface charge and size, impact their absorption
and translocation in plants [1]
• Uptake processes:
• NPs are first adsorbed on the roots’ surface and then move via a series of barriers to enter
the plant’s vascular system [1]
• Uptake pathways:
• NPs can penetrate the root epidermis via apoplastic or symplastic pathways, with the
symplastic pathway involving migration through plasmodesmata [1]
• Barriers to uptake:
• The root cuticle layer and cell wall pores serve as barriers for NPs, with the Casparian strip
around the vascular system being the most significant barrier in the apoplastic pathway [1]
MACRONUTRIENT NFs: THEIR FUNCTION AND IMPACT ON
PLANTS
• Essentiality of fertilizers:
• Fertilizers are essential for plant development, increasing crop productivity and quality by
providing necessary macronutrients such as N, P, and K [1]
• Challenges with traditional fertilizers:
• Most nutrients are poorly absorbed by plant roots, leading to the application of excessive
fertilizer quantities, which has adverse effects on soil, water, and the environment [1]
• Role of Nanofertilizers (NFs):
• NFs enhance fertilizer NUE (Nutrient Use Efficiency), improve plant productivity, and reduce
the harmful effects of traditional fertilizers, contributing to sustainable agriculture [1]
• Precision nutrient release:
• NFs release nutrients precisely at the plant roots, reducing nutrient losses by avoiding rapid
variations in soil composition [1]
• Materials and carriers:
• NFs are formed from various materials and carriers, including hydroxyapatite NPs, zeolite,
mesoporous silica NPs, N, Cu, Zn, Si, C, and polymeric NPs [1]
MACRONUTRIENT NFs:
THEIR FUNCTION AND
IMPACT ON
PLANTS
NITROGEN NFs
•Vital role of nitrogen:
•
Nitrogen is essential for plant growth as it is present in amino acids, proteins, DNA, ATP,
chlorophylls, and cellular structural units, supporting metabolic activities and regulatory
mechanisms [1]
•Nitrogen absorption:
•
Plants absorb nitrogen mainly as NO3- and NH4+ [1]
•Drawbacks of traditional N fertilizer:
•
Excessive volatilization and leaching of nitrogen after application in the field pose significant
challenges [1]
•Benefits of Nitrogen-based Nanofertilizers (NFs):
•
NFs can deliver a steady supply of nitrogen, reducing volatilization and leaching, increasing
nutrient absorption, and improving plant performance and yield [1]
•Example of NPK-coated NFs:
•
Application of NPK-coated NFs on coffee plants resulted in increased nutrient uptake, growth,
leaf numbers/area, and leaf gas exchange capacity [1]
PHOSPHORUS NFs
• Importance of phosphorus:
•
Phosphorus is essential for plant performance as it is involved in energy transfer
molecules such as ATP, ADP, phospholipids, and sugar phosphate, influencing
photosynthetic capacity, respiration, and DNA biosynthesis [1]
• Impact of phosphorus availability:
• The availability of phosphorus affects plant growth and production efficiency [1]
• Challenges with conventional P fertilizers:
• Lengthy release time and high soil fixation reduce the availability of phosphorus
in synthetic fertilizers [1]
• Benefits of Phosphorus-based Nanofertilizers (NFs):
• NFs can provide a sustained release of phosphorus over 45–55 days, compared
to the 10-day release of conventional synthetic fertilizers, thereby improving
nutrient use efficiency (NUE) of phosphorus in plants [1]
• Enhanced plant performance:
• Biosafe NFs that serve as a phosphorus source were found to enhance biomass,
production, and crop quality, contributing to overall plant performance [1]
POTASSIUM NFs
• Potassium (K) emerges as a vital element in plant
physiology, following nitrogen and phosphorus.
• It serves as a critical component in numerous
physiochemical functions essential for proper plant
development.
• Potassium is intricately involved in various processes
within plants, including stomatal opening,
photosynthetic responses, translocation of
photosynthates, protein synthesis, maintenance of
ionic balance, water interactions, and enzymatic
mechanisms (Preetha and Balakrishnan, 2017).
MICRONUTRIENT NANOFERTILIZERS AND
THEIR ROLE
ZINC NFs
• Zinc (Zn) serves as a structural component and co-factor for numerous proteins and enzymes, playing a
pivotal role in facilitating proper plant growth.
• Various essential processes within plants, including auxin regulation, protein metabolism, carbohydrate
biosynthesis, and defense against biotic and abiotic stresses, rely on zinc (Broadley et al., 2007).
• Zinc Nanofertilizers (NFs) formulated with ZnO exhibit higher efficiency and cost-effectiveness compared to
synthetic fertilizers (Khan et al., 2018; Seleiman et al., 2020). Consequently, they are increasingly utilized in
modern agricultural systems (Seleiman et al., 2020).
• Zinc NFs can be applied through soil mixing, seed priming, and foliar application, offering versatility in
agricultural practices.
• However, excessive concentrations of trace metals like zinc can negatively impact plant growth by inducing
metabolic disruptions (Ali et al., 2020).
• Studies have demonstrated that the use of zinc NFs improves crop germination, seedling growth, and overall
productivity (Seleiman et al., 2020).
• Among zinc NFs, those formulated with ZnO are the most commonly employed in modern agriculture due to
their effectiveness and affordability. They are utilized through foliar application, soil mixing, and seed
priming, contributing to enhanced crop yield and quality.
IRON NF
• Iron (Fe) is essential for various vital processes in plants, including chlorophyll synthesis, DNA
synthesis, chloroplast ultrastructure maintenance, respiration, and other metabolic pathways.
• Despite being required in small quantities, both deficiency and excess of iron can disrupt
physiological and metabolic functions in plants (Palmqvist et al., 2017).
• In well-watered soils, iron availability is generally high. However, at neutral pH levels, iron forms
insoluble ferric complexes, rendering it inaccessible to plants.
• Fe-enriched fertilizers can aid in making iron more accessible to plants, addressing deficiencies.
• Research suggests that iron Nanofertilizers (NFs) have shown promise in improving germination
and growth in various crops compared to traditional iron sources.
• For instance, the development of spinach was facilitated by iron pyrite nanoparticles (Srivastava
et al., 2014), while field studies demonstrated improved root growth in peanuts treated with iron
NPs (Rui et al., 2016).
• Fe NFs present a potential alternative source of iron, particularly beneficial in soils with low iron
levels, offering improved plant growth and development.
MANGANESE NFs
• Manganese (Mn) is a micronutrient essential for various crucial processes in plants, including
nitrogen metabolism, photosynthetic capacity, fatty acid synthesis, ATP production, and protein
synthesis (Palmqvist et al., 2017).
• However, excessive manganese can pose risks to certain plant species, particularly in acidic soils,
depending on the chemical characteristics.
• Despite this, manganese plays a crucial role in enabling plants to cope with diverse stress
conditions.
• Application of manganese has been demonstrated to enhance the growth and productivity of
several crops, including wheat, maize, sugarcane, soybeans, and common beans (Fageria, 2001;
Dimkpa and Bindraban, 2016).
• Manganese Nanoparticles (NPs) exhibit specific mechanisms that enhance plant photosynthetic
efficiency. For instance, Mn NPs bind to the chlorophyll-binding protein (CP 43) of photosystem-II,
thereby increasing electron transport chain efficiency and overall photosynthetic performance
(Pradhan et al., 2013).
• Plants treated with manganese NFs show improved nitrogen uptake and enhanced metabolic
activities compared to those treated with conventional manganese fertilizers.
COPPER NFs
• Copper (Cu) serves as a vital component of regulatory proteins involved in key plant
processes such as photosynthesis and respiration. It acts as a cofactor for antioxidant
enzymes like Superoxide Dismutase (SOD) and Ascorbate Oxidase (AsO).
• Imbalances in copper levels can lead to various problems in plants, including chlorosis,
necrosis, stunted growth, and reduced seed, grain, and fruit yield, ultimately resulting in
low crop yield (Rai et al., 2018).
• The availability of copper in soil is influenced by the amount of organic matter present.
Copper Nanoparticles (NPs) in soil hold significant potential due to their large surface
area, high solubility, and reactivity (Hong et al., 2015).
• Studies have shown that CuO NPs applied in the field can enhance germination
percentages and root development in crops like soybeans and chickpeas (Adhikari et al.,
2012).
• While copper Nanofertilizers (NFs) have the potential to improve biochemical and yield
characteristics of crops significantly, their usage must be approached with caution to
prevent adverse effects.
SILICON NFs
• Silicon (Si) occupies a unique position between essential and nonessential components for plant
fitness, offering some notable benefits to plants (Rastogi et al., 2019; Seleiman et al., 2019).
• While silicon is abundant in the Earth's crust, plants primarily absorb it in the form of mono-silicic
acid from the soil.
• Si has garnered significant attention recently due to its diverse functions in enhancing plant
resistance to various stresses.
• Studies have demonstrated that silicon can improve plant adaptation strategies to ion toxicity,
temperature fluctuations, drought, chilling, UV radiation, waterlogging, and salinity stresses
(Rastogi et al., 2019; Seleiman et al., 2019).
• Combining SiO2 with organic fertilizers has been shown to enhance overall plant performance
(Janmohammadi et al., 2016; Seleiman et al., 2020).
• Si Nanoparticles (NPs)-based nanosensors and nanozeolites are successfully utilized in agriculture
for monitoring soil moisture levels and increasing soil water retention (Rastogi et al., 2019).
• Si NPs can serve as fertilizers for plants requiring silicon supplementation or as nano-carriers to
support the advancement of sustainable agriculture practices.
BORON NFs
• Boron (B) plays a crucial role in several physiological processes in plants, including
the formation of cellular walls, translocation of photosynthetic products from
leaves to active sites, and the development of flowers and fruits (Davarpanah et
al., 2016).
• Studies have demonstrated that Boron Nanofertilizers (NFs) or Nanoparticles
(NPs) can significantly enhance plant growth and productivity (Ibrahim and Al
Farttoosi, 2019).
• For instance, Genaidy et al. (2020) applied as-sprayed nano-boron on olive plants,
resulting in the highest fruit yield with the highest seed oil content.
• Taherian et al. (2019) utilized B nanofertilizers on calcareous soil for alfalfa plants,
leading to high crop yields with good forage quality.
• Overall, the application of Boron NFs holds promise in increasing crop production,
offering potential benefits for agricultural sustainability and productivity.
Nanofertilizers
• Traditional fertilizers exhibit low nutrient use efficiency, leading to
significant losses during application. For instance, in China, a considerable
portion of nitrogen fertilizer is lost through volatilization and leaching,
contributing to environmental issues such as eutrophication (Kah et al.,
2019).
• Nanofertilizers offer several advantages over traditional fertilizers:
• Enhanced solubility: Nanofertilizers have higher solubility due to their smaller size
and larger surface area, facilitating better nutrient uptake by plants.
• Improved penetration power: Their small size enables nanofertilizers to penetrate
plant tissues more effectively, allowing for easier uptake by plants.
• Controlled release and target specificity: Nanofertilizers can be designed with a slow
release rate and targeted delivery, preventing overuse of fertilizers and minimizing
environmental impact.
Nanofertilizers
• Ways of applying nanofertilizers:
1. Direct application: Various nanomaterials like
fullerenes, carbon nanotubes, nano-TiO2,
nano-SiO2, ZnO, etc., can be directly applied at
different growth stages of crops, either
independently or in conjunction with
traditional fertilizer practices (Millan et al.,
2008).
2. Nanoencapsulations: Fertilizers are
encapsulated within nanostructures designed
to release nutrients in response to specific
signals, such as environmental cues or induced
stimuli (Aouada et al., 2015).
3. Complex delivery systems: Nanocapsules
incorporated within matrices of organic
polymers, either of biological or chemical
origin, serve as carriers for delivering
nanofertilizers in a controlled manner.
continue
Nanopesticides
• Traditional pesticides encounter several issues, including
inefficiency, toxicity to non-target organisms,
development of resistance, persistence, and potential
environmental accumulation.
• It's estimated that a significant portion of applied
pesticides (10–75%) fails to reach the intended target.
• Nanopesticides offer superior effectiveness compared to
traditional pesticides due to several factors:
• Enhanced dispersion and bioavailability:
Nanopesticides exhibit improved dispersion and
bioavailability, allowing for better coverage and
penetration.
• Improved spread and adhesion: They enhance
spread and adhesion over surfaces, ensuring better
efficacy.
• Reduced cytotoxic and phytotoxic effects:
Nanopesticides show reduced cytotoxicity and
phytotoxicity, minimizing harm to non-target
organisms and plants.
• Lack of non-target effects: Unlike traditional
pesticides, nanopesticides do not have non-target
effects, further enhancing their safety and
effectiveness (Huang et al., 2018).
Nanopesticides
• Nanopesticides can be prepared using various methods:
• Adsorption of pesticide on the surface of
nanoparticles.
• Attachment of pesticide to nanoparticles using
linkers.
• Encapsulation of pesticide in nanomaterial-made
shells.
• Entrapment of pesticide inside a nanopolymeric
matrix.
• These nanopesticides release the pesticides in response
to specific environmental signals, allowing for controlled
and targeted pest management (Kumar et al., 2019).
• Si-NPs as Pesticides
Nanoherbicides
• The herbicide market in agriculture is a significant multi-billion-dollar
industry.
• Conventional non-nanoherbicides encounter various issues, including
dissipation through vaporization, soil degradation, non-target effects,
and increased weed resistance (Abigail and Chidambaram, 2017).
• Nanoherbicides offer a promising new strategy to address these
challenges and improve weed management in agriculture.
Use of Ag-NPs in Agriculture
• AgNP-Soil Interaction
Enviromental Applications
Books
Nanotechnology in Renewable
Energy
Conversion and Storage Process
Modern Nanotechnology
Volume 2: Green Synthesis, Sustainable
Energy and Impacts
Part II
Types of Sustainable Green Energy Source
• Nanoscience and nanotechnology advancements have revolutionized various fields.
• Capacity to manipulate atomic and molecular materials has led to new possibilities.
• Research offers solutions to energy, environmental, and transportation challenges.
• Growing demand for clean energy drives research in new material technologies.
• Alternative fuels and energy storage innovations pose serious threats to petroleum-based fuels.
• Nanomaterials enhance energy conversion and storage systems.
• Evolution of lithium-ion batteries is a significant achievement in contemporary materials
electrochemistry.
• Supercapacitors play a critical role in maintaining system voltage under increased loads.
• Fuel cell technologies offer promising applications, especially in mobile power sources and
electrical energy production.
• Nanostructured materials enhance fuel cell efficiency at low temperatures.
• TiO2 photochemistry shows potential for environmental protection and green energy production.
• TiO2 nanostructures improve the photoelectrochemical properties of solar energy materials.
Renewable Energy Conversion: Sustainable
Green Processes
• Escalating energy crisis and environmental degradation due to population growth and
industrialization.
• Non-renewable fossil fuels (oil, natural gas, coal) are depleting rapidly, leading to environmental
harm.
• Need to shift towards renewable energy sources (solar, wind, geothermal, hydropower, biofuels).
• Solar power emerges as an effective renewable energy source, but cost reduction remains a
challenge.
• Scientists focus on novel technologies like catalysis, solar cells, Li-ion batteries, and
supercapacitors.
• Research aims to address environmental degradation and energy scarcity.
• Nanostructured materials play a crucial role in developing sustainable energy technologies.
• Various nanostructures (1D, 2D, 3D) are utilized in catalysts, solar cells, and energy storage
devices.
Batteries
• Portable gadgets rely on various energy
devices for power supply.
• Components of lithium batteries (LBs)
include anode and cathode electrodes,
separator, and electrolyte.
• Liquid analytes are commonly used in LBs
due to high ionic conductivities.
• Challenges with liquid analytes include
leakage, flammability, and toxicity.
• Polymer electrolytes offer potential as
replacements for liquid electrolytes due
to their wider electrochemical window
and superior thermal resilience.
Supercapacitors
• Renewable energy sources are environmentally friendly and sustainable.
• Urgent need for energy storage systems to support the expansion of renewable energy.
• Electrochemical energy storage systems offer high efficiency, affordability, and adaptable
capacities.
• Rechargeable batteries are widely used but have drawbacks such as lower power
densities and reduced cycle lifespan.
• Problems with thermal maintenance and environmental protection are also present.
• Supercapacitors are emerging as promising alternatives for electrical energy storage.
• They offer quick charge/discharge speeds, long cycle lives, lightweight design, and
environmental friendliness.
• Supercapacitors complement rechargeable batteries and demonstrate enormous
promise for commercial energy storage solutions.
Technology of Supercapacitors (SCs)
• Supercapacitors, also known as ultracapacitors or electrochemical
capacitors, store electrical energy.
• They operate by separating ionic and electronic charges at the electrodeelectrolyte interface, forming an electric double layer (EDL).
• EDL capacitors have a thin layer with a large surface area, allowing for high
specific capacitances and bandwidth.
• Supercapacitors can be categorized into different types, including electric
double-layer capacitors (EDLCs), pseudocapacitors (PCs), and hybrid
supercapacitors (HSCs).
• EDLCs have almost unlimited cycles due to the absence of chemical or
physical changes during repetitions.
• PCs and HSCs may have shorter lifespans due to Faraday reactions during
charge and discharge.
Technology of Supercapacitors (SCs)
• Supercapacitors maintain high capacitive performance and storage
retention rates, up to 99%.
• They are safe to use and easy to reuse, requiring less electrolyte
compared to rechargeable batteries.
• Supercapacitors find applications in various fields, including
renewable energy storage, transportation (electric vehicles),
consumer electronics, and power backup systems.
• Their high power density and quick charge/discharge capabilities
make them ideal for applications requiring rapid energy transfer.
Fuel Cells
• Fuel cells are electrochemical devices that convert chemical energy into electrical
energy.
• They are essential for green, renewable, and sustainable energy resources.
• Fuel cells are categorized based on the electrolyte they use, including solid oxide
fuel cells, molten carbonate fuel cells, phosphoric acid fuel cells, alkaline fuel
cells, and polymer electrolyte membrane fuel cells (PEMFCs).
• Proton Exchange Membrane (PEM) Fuel Cells
• PEM fuel cells are highly efficient, have high power density, and produce minimal
pollution.
• They find applications in micropower, fixed and portable electricity, and
transportation.
• Research and development on PEM fuel cells have improved stack performance
and reduced costs over the years.
Fuel Cells
• High cost and poor reliability/durability are major challenges hindering
commercialization.
• Fuel cell catalysts, particularly platinum (Pt)-based catalysts, and catalytic
layers are critical areas for improvement.
• Efforts focus on developing affordable, functional, and durable catalysts to
enhance performance and lower costs.
• Pt-based nanoparticles are the current best catalysts for PEM -Proton
Exchange Membrane -fuel cells, but they have disadvantages such as high
cost and lack of stability.
• Research explores alternatives to platinum group metals (PGM), including
supported PGM types, bimetallic alloyed catalysts, transition metal
macrocycles, and transition metal chalcogenides.
Nanomaterials for Photocatalysis
• Photocatalysis is a technique used in various fields like physics,
chemistry, and engineering.
• It offers several benefits, including inexpensive electricity generation,
environmental cleanup, and CO2 reduction.
• Photocatalysis involves the absorption of light by a solid substance,
initiating a photocatalytic process, often occurring at the surface of a
semiconducto
• Semiconductor photocatalysts, such as bismuth oxide (BiOX) and
bismuth iodide oxide (BiOI), exhibit exceptional photocatalytic activity.
• BiOX's multilayer structure prevents charge carrier recombination,
while BiOI's low band gap enhances visible light absorption.
• Significant applications include energy generation and environmental
pollution management, with various inorganic semiconductors serving
as dynamic catalysts.
Nanomaterials for Photocatalysis
• Graphitic Carbon Nitride (g-C3N4)
• g-C3N4 is a promising photocatalyst with unique physical and chemical
properties.
• It offers a good price-to-performance ratio, strong electrical structures, and
superior light-absorbing abilities.
• A good photocatalyst should be safe, reliable, cost-effective, and highly
photoactive, with suitable band gap energies for photocatalysis.
• Nanostructured Materials in Photocatalysis
• Nanostructured materials, like porous nanospheres, nanowires, nanoparticles,
nanorods, and nanotubes, offer enhanced chemical and physical characteristics.
• These materials provide more surface active sites, enabling improved material
selection and photocatalysis applications.
• Semiconductors with nanostructures exhibit quantum confinement and
plasmonic absorption, contributing to efficient solar energy capture.
Carbon Capture and Storage
• In 2020, the global average annual concentration of CO2 reached a record high of 412.5 ppm, highlighting the urgent need to
reduce CO2 emissions.
• The Intergovernmental Panel on Climate Change (IPCC) emphasizes the importance of achieving net-zero CO2 emissions by 2050 to
mitigate the effects of climate change.
• Carbon capture and storage (CCS) technology aims to collect CO2 emissions and securely store them underground to prevent their
release into the atmosphere.
•
Geological Storage of CO2
• CCS involves collecting CO2 either directly from emission sources or from the air, compressing it, and storing it underground in
impermeable rock formations.
• Deep saline aquifers, deep coal seams, and used hydrocarbon reserves are potential storage sites for captured CO2.
• Long-term monitoring is necessary to ensure the effectiveness and safety of geological storage.
• Carbon Capture and Utilization (CCU)
• Captured CO2 can also be utilized in various chemical processes, such as producing synthesis gas (syngas) or synthetic methanol.
• CCU offers potential applications in chemical industries for producing various chemicals and fuels, contributing to a circular
economy approach
Carbon Capture and Storage
Technologies for CO2 Capture
Three main technologies for CO2 capture include oxy-fuel combustion, post-combustion capture, and pre-combustion capture.
Post-combustion capture methods, such as absorption using amine-based solvents or membrane-based methods, are simpler to
integrate into existing plant infrastructure.
Direct Air Capture (DAC)
DAC technology captures CO2 directly from the air, offering a solution for emissions from mobile sources.
Chemisorbent substances are used to extract CO2 from ambient air, contributing to efforts to achieve net-zero CO2 emissions
Integration with Chemical Processes
Integrating CO2 capture with chemical reactions can improve process efficiency and reduce CO2 emissions.
The development of low-cost materials and energy-efficient CO2 capture systems presents economic opportunities for carbon
capture technology.
Future Directions
Future research should focus on developing advanced CO2 adsorbents and catalysts to enhance process intensification and efficiency.
Improvements in stability, selectivity, and performance of adsorbents and catalysts are crucial for the successful integration of CO2
capture with chemical processes.
Application of Nanotechnology
in Bioenergy Production from Algae
and Cyanobacteria
Bioenergy
Bioenergy from Algae and Cyanobacteria
• Biomass energy can be derived from various sources such as cellulose,
lignocellulose, proteins, starch, and lipids from biomass obtained from
plants and microbes.
• Biomass-derived biofuels including biodiesel, bioalcohol, biogas, and
biocrude offer remarkable alternatives to petroleum-based fuels.
• Advancements in biomass energy have progressed from edible crops (first
generation) to non-edible oil crops (second generation) and now to
microorganisms like algae and cyanobacteria (third generation).
• Fourth-generation bioenergy combines biofuel production with CO2
sequestration, offering a promising sustainable mode of energy production.
Bioenergy
Algae and cyanobacteria are highly efficient in photosynthesis, making them
preferred sources of biomass for bioenergy production.
Microalgae/cyanobacteria offer advantages such as high photosynthetic
efficiency, rapid biomass accumulation, year-round availability, and the
ability to grow in various environments including industrial effluents and
seawater.
Conversion of algal biomass into biofuels involves physicochemical,
biochemical, and thermochemical processes, producing biodiesel,
bioethanol, biomethane, biohydrogen, and synthetic fuels.
Algae/cyanobacteria can help reduce carbon footprint by utilizing carbon
dioxide during growth, with microalgae accumulating oil content exceeding
50% of dry weight.
• Bioenergy production from algae/cyanobacteria involves several
phases: biomass production, macromolecule accumulation, harvesting,
separation, and transformation into bioenergy.
• Nanotechnology plays a significant role in each phase of the algal
biorefinery process, leading to advancements in biofuel production and
reducing life-cycle costs.
• Integration of nanoparticles (metallic, hybrid, functionalized magnetic,
aminoclay), plasmonic film filters, and nanobubbles enhances microalgal
biorefineries.
• Nanoparticles such as nanofibers, nanotubes, nanodroplets, and
nanosheets impact microalgal proliferation, co-product development, and
bioenergy yield.
• Nanoparticles promote biomass productivity and can induce stress to
accumulate required cell storage products quickly.
• Nanomaterials serve as carriers of chemicals during extraction
processes and catalysts during biofuel conversion processes.
• Multifunctional nanoparticles improve conversion efficiency,
purification, and biofuel quality in microalgal biorefineries.
• Physicochemical characterizations of nanoparticles for efficient
bioenergy conversion are emphasized, along with considerations for
nanoparticle recovery, reusability, and recycling to address environmental
concerns.
Nanotechnology for Biomass Production
• Biomass production and the generation of multiple products in a
biorefinery are dependent on various management strategies.
• Key factors influencing biomass production include atmospheric scattering,
absorption, latitude, weather, physical orientation, photosynthetically
active radiation (PAR), light saturation, photosynthetic efficiency,
biosynthesis, maintenance, harvesting, and processing.
• Optical engineering techniques are essential to maximize energy
conversion efficiency for biomass production in biorefineries.
• Closed photobioreactors are commonly used for cultivating
algae/cyanobacteria to ensure quality biomass production.
• Productivity may decline as cell density increases due to self-shading,
reducing illumination reaching each cell.
Nanotechnology for Biomass Production
• Surface plasmon resonance (SPR) of nanoparticles enhances photosynthetic efficiency and
productivity in closed photobioreactors.
• Fabricated LEDs with gallium aluminum arsenide nanoparticles can achieve the required
illumination properties and photoconversion efficiency.
• Excitation of cyanobacteria with gold surface plasmon increases biofilm thickness and cell density
in the evanescent fields, leading to enhanced biomass accumulation.
• Silver plasmonic layers scatter blue light towards microalgal cells/cyanobacteria, resulting in
increased biomass production.
• Nanoparticle structure, such as prolate ellipsoids or spheres, can impact
microalgal/cyanobacterial growth differently.
• Nanoparticles like Zeolitic Imidazolate Framework-8 enhance biomass production by increasing
CO2 dissolution and promoting growth, although higher doses may cause cell toxicity.
• Efficient mass transfer of CO2 to microalgal cells can be achieved by designing photobioreactors
with appropriate nanoparticle structures.
Nanotechnology for Biomass Production
Nanotechnology for Biomass Harvesting
Biodiesel
Enhancement of Lipid Productivity:
Nanocatalysts play a crucial role in increasing lipid yield by reducing reaction
parameters such as temperature, time, catalyst ratio, and methanol
concentration.
Various microalgae species such as Chlorella vulgaris, Chlorococcum
humicola, and Botryococcus braunii are suitable for biodiesel generation due
to their high lipid content.
Nanoparticles like MgSO4 have been utilized to enhance lipid yield in
microalgae cells, while supplementation of carbon nanotubes, Fe2O3, and
MgO nanoparticles in Scenedesmus obliquus has shown promising results in
increasing lipid productivity.
However, it's important to note that excessive nanoparticle concentration
may inhibit cell growth
Biodiesel
• Nanomaterials in Transesterification:
• Nanomaterials offer efficient extraction of oil without damaging cells, thereby
reducing the overall cost of biomass production, harvesting, and extraction.
• CaO is highlighted as an economical and sustainable nanocatalyst for biodiesel
production, with its mechanism involving hydrogenation and acidic side change by
oxides.
• Enzymatic hydrolysis integrated with magnetic nanoparticles facilitates lipid
extraction, while nanoparticles of calcium compounds and silica enhance microalgal
growth without affecting biofuel production.
• Examples of Nanocatalysts and Their Effects:
• Examples include Ca(OCH3)2, graphene/graphene oxide, Fe/Fe2O3 nanoparticles
with dispersed carbon nanotubes, and carbon nanotubes impregnated with Na2O.
• These nanocatalysts demonstrate high conversion efficacy and catalytic properties,
making them valuable in transesterification processes for biodiesel production.
Bioalcohol
• Algal and Cyanobacterial Sources of Polysaccharides:
•
•
Various algae and cyanobacteria species, such as Chlorella vulgaris, Botryococcus braunii, and Spirulina platensis, accumulate polysaccharides suitable for
bioalcohol production.
These polysaccharides are valuable feedstocks for bioethanol production due to their high yield and digestibility.
• Nanotechnology in Fermentation Steps:
•
•
Nanotechnology plays a crucial role in all fermentation steps, including pre-treatment, catalytic hydrolysis, saccharification, and purification, offering high
efficiency and low production costs.
Different nanotechnologies employed in lignocellulosic biomass conversion into simple sugars include nanoshear hybrid alkaline technique (NSHA),
nanofibers, nanofiltration, nanotubes, and nanosensors.
• Commercial Viability of Bioethanol Production:
•
•
•
Bioethanol production is currently more commercially viable due to the availability of feedstocks, reduced harmful emissions, and lower production costs.
Addition of nanoparticles in bioreactors facilitates instantaneous saccharification, accelerating bioethanol production while reducing acetic acid formation.
Nanoparticles immobilize enzymes and break down complex sugars required for fermentation, enhancing catalytic efficiency and reducing costs.
• Nanoparticles in Biomass Pre-treatment:
•
•
•
Nanoparticles such as silver and acid-functionalized magnetic nanoparticles are used for biomass pre-treatment, providing better stability and enzyme
activity.
Reusable nanoparticles like methyl-functionalized silica increase bioethanol production, while Fe3O4/alginate composites offer stability and higher
theoretical yields.
Pt-Ru/RGO nanoparticles enhance biomass and ethanol production in microalgae, demonstrating increased ethanol yield at optimal nanoparticle
concentrations
Biohydrogen
• Biohydrogen is recognized as an environmentally friendly energy source.
• Algae and cyanobacteria play a crucial role in biohydrogen production through various
metabolic pathways.
• Biohydrogen Generation Processes:
• Biophotolysis (direct and indirect) and fermentation (dark and photo) are the two main
processes involved in biohydrogen evolution from algae and cyanobacteria.
• Studies have shown that dark fermentation can increase biohydrogen production, as
demonstrated in experiments with cyanobacterium Anabaena sp.
• Role of Nanoparticles in Biohydrogen Production:
• Nanoparticles significantly enhance both the yield and rate of biohydrogen evolution.
• The size of nanoparticles plays a crucial role, with smaller nanoparticles (<42 nm) improving
hydrogen yield.
• Addition of iron nanoparticles in dark fermentation processes has been shown to increase
biohydrogen production.
Biohydrogen
• Types of Nanoparticles Used:
• Various nanoparticles, including Au, Ag, Cu, Pd, Ni, Fe, silica, Ti, and carbon
nanotubes, have been employed to enhance biological hydrogen evolution.
• Fe0 nanoparticles have been particularly effective, increasing hydrogen production
by modulating metabolic pathways.
• Nickel ferrite nanoparticles and Ni NPs have also shown promising results in
biohydrogen production through anaerobic digestion of algae.
• Photobioreactor for Biohydrogen Production:
• Photobioreactors can be constructed to maximize biohydrogen production, as
demonstrated in studies cultivating Chlamydomonas reinhardtii in a tubular
photobioreactor under artificial light.
• Uniform distribution of illumination in the photobioreactor can be achieved with the
use of silica nanoparticles
Biomethane
• Resource Recovery Technology for Biomethane Generation:
•
•
•
Geng et al. (2020) proposed a resource recovery technology using anaerobic digestion for biomethane production from algal
sludge.
Nanoscale zero-valent iron (nZVI) significantly increased methane production without pretreatment, achieving a 1.46-fold
increase at a concentration of 20 g·ZVI/g·TS.
In substrate models, nanoparticles notably enhanced hydrolysis rates, indicating their potential to improve anaerobic
digestion efficiency.
• Enhancement of Methane Formation:
•
•
Nanoscale Fe powder and Fe2O3 have been shown to enhance methane formation in anaerobic digestion by up to 40% and
98.63%, respectively.
These nanoparticles promote microalgal growth and increase biomethane potential, contributing to more efficient
bioenergy production.
• Conversion of Biomethane:
•
•
Biomethane produced from microalgae can be converted into carbon and hydrogen, providing versatile energy resources.
Biogas generated from anaerobic digestion can be utilized for electricity generation, offering a sustainable energy source.
• Pretreatment for Biogas Generation:
•
•
Pretreatment methods are employed to enhance biogas production efficiency.
El Nemr et al. (2021) investigated various pretreatment techniques for cell wall breakage of alga Ulva intestinalis, with
Fe3O4 combined with microwave treatment showing high efficiency in releasing biogas.
Nanotechnology in bioremediation
• Save the Sea
• Water Cleanliness
• Cleaning the Air
Green Synthesis of Visible Light-Driven g-C 3 N 4 Based Composites for Wastewater Treatment
• The graphitic carbon nitride g-C3N4 (GCN) is a metal-free polymer ntype semiconductor.23
• Because of its higher activity and visible light absorption, GCN is
evolved as a trending material
• in photocatalysis. The structure of GCN is composed of only two
elements, namely carbon and
• nitrogen.24 The higher chemical and thermal stability is ascribed to the
existence of the strong cova• lent bond between carbon and nitrogen in the conjugated structure of
the GCN.25 The bandgap of
• 2.7 eV makes it favourable for visible light harvesting.26 The GCN also
possesses higher electrical
• conductivity due to the delocalized conjugated structure composed of
stacked carbon nitride layers
• connected by means of tertiary amines.25 Generally, the GCN is
prepared using urea, melamine,
• thiourea, cyanamide, dicyandiamide, etc., due to higher carbon and
nitrogen contents.27
Green Synthesis of Visible Light-Driven g-C 3 N 4 Based Composites for Wastewater Treatment
•
The main advantages of the GCN are non-toxicity, greater stability, easy fabrication, abundance,
•
higher activity in visible light, and stronger reduction ability.28 These special properties permit
the
•
usage of GCN for different applications in the areas of catalysis for both energy and
environmental
•
remediation, biomedical applications, hydrogen fuel generation, chemical transformation,
etc.29–34
•
The higher recombination ratio of electron-hole pairs, incomplete utilization of the visible light
•
absorption, the lower surface area of the GCN, lesser availability of the active sites for the
interfa-
•
cial reactions, greater degree of the condensation of monomers, and slow surface kinetics limit
the
•
usage of GCN as a photocatalyst.24,35,36 Several studies emphasized different methods to
overcome
•
the problems associated with the GCN-based photocatalysts. For example, the developments of
•
heterojunctions are beneficial in promoting charge transfer, mobility, and separation
efficiency.31,37
•
The doping using metals and non-metals improves visible light absorption to a greater extent.
Green Synthesis of Visible Light-Driven g-C 3 N 4 Based Composites for Wastewater Treatment
• Heterogeneous Photocatalysis Steps:
•
•
•
The photocatalytic degradation process involves five steps: I.
Diffusion of organic pollutants to GCN surface. II. Adsorption of
pollutants onto GCN surface. III. Photochemical reaction
between light and catalyst, producing reactive species like
oxygen radicals. IV. Desorption of reaction products from GCN
surface. V. Removal of products from solution bulk.
The slowest step determines overall reaction rate, with Steps I
and V typically faster than Steps II, III, and IV.
Steps II and III, involving powerful OH oxidizing agents, do not
significantly influence reaction rate.
• Photocatalytic Degradation Mechanism:
•
•
•
Upon visible light illumination, electrons move from valence
band to conduction band, generating holes in valence band.
Photogenerated holes are trapped by hydroxyl ions, forming
hydroxyl radicals, potent oxidants responsible for pollutant
mineralization.
Trapped oxygen may suppress hole recombination, while limited
oxygen supply can accelerate electron-hole recombination.
•Three essential criteria for nanoparticle synthesis:
• Eco-friendly solvent selection
• Efficient reducing agent
• Non-toxic material for stabilization
•Routes: Physical, chemical, biological
•Chemical methods: Hazardous, expensive
•Biological methods: Safe, eco-friendly, biocompatible
• Advantages:
• Cost-effectiveness and scalability
• Mild operating conditions
• Eco-friendliness
•Green synthesis of photocatalysts:
• Utilizes plant extracts or microorganisms
• Abundant and low-cost sources
• Presence of various chemicals aids in nanoparticle production
•Advantages of using plant extracts:
• Non-toxic capping agent
• Environmentally friendly reducing agent
• Suitable solvent selection
•Examples of green synthesis:
• Cu2O nanospheres-decorated GCN using Citrus limon leaves
• Eriobotrya japonica-assisted GCN preparation
•Preparation of Ag@GCN composites using Sapindus emarginatus bark
extract:
• Dried and ground bark powder used to prepare aqueous extract
• Extract mixed with GCN powder and Ag(NO3)
• Refluxed at 65°C, then dried and grounded
•Green synthesis of GCN/Ag nanocomposites with grape seed extract:
• Grape seed extract mixed with GCN supernatant and silver nitrate
• Heated at 95°C for 20 minutes
• Grape seed acts as reducing and stabilizing agent
•Sol-gel method for DyFeO3/CuO/GCN using Capsicum annuum extract:
• Capsicum annuum acts as chelating agent controlling crystal growth
•Preparation of tertiary CeO2/GCN/Ag photocatalyst with Piper betle extract:
• Extract mixed with GCN, silver nitrate, and cerium nitrate
• Combusted at 500°C
•One-pot GCN/Bi2O3 synthesis using Eichhornia crassipes leaf extract and
surfactant:
• Forms heterojunction between GCN and bismuth oxide
• SEM and TEM confirm structure and spacing
•Bio-surfactant-mediated synthesis of Au/GCN with Averrhoa carambola leaf:
• Leaf extract mixed with HAuCl4, then with GCN suspension
• Produces spherical gold nanoparticles
• Green lead commonly utilized in GCN-based composite preparation
•reen synthesized photocatalysts offer versatility and unique
properties for environmental remediation.
•Used as photocatalysts or adsorbents to remove various
contaminants from wastewater.
•Limited studies on green synthesized GCN for wastewater
treatment.
•Examples of applications:
• Adithya et al.: Utilized green synthesized Gd2O3/GCN to
remove Amaranth and Congo red dyes.
• Achieved 85% and 95% removal, respectively, within 1
hour of visible light irradiation.
• Phenomenal catalytic activity attributed to inhibited
electron-hole recombination and improved charge
carrier separation.
• GCN/Bi2O3 heterojunction employed for malachite green
removal, achieving 98.7% removal using visible light.
• .
•
•
•
•
•
• Showed 78% reduction in malachite green concentration
(20 ppm) via total organic carbon analysis.
Green synthesized GCN/Ag3PO4 exhibited 96% methylene
blue removal within 10 minutes of visible light irradiation.
• Demonstrated reusability for up to five cycles while
maintaining activity.
Green GCN structures removed 100% of rhodamine B under
visible light within 15 minutes, with extended reuse.
Eriobotrya japonica-assisted green synthesized GCN showed
2.6 times higher removal efficiency for rhodamine B
compared to bare GCN.
Green wet ball milling-assisted GCN nanosheets achieved
95% rhodamine B elimination within 120 minutes, potentially
due to increased active sites.
Green synthesized Au@GCN removed 86% methyl orange
within 180 minutes using visible light
•Savunthari et al.: Green synthesized lignin nanorods/GCN composites
removed triclosan from water.
• Achieved 99.5% removal within 90 minutes, attributed to synergistic
effect between lignin and GCN.
• Reduction in bandgap from 2.86 to 2.83 eV due to changes in
morphology and microstructures.
•Dou et al.: Green synthesized sulphur-doped GCN eliminated oxytetracycline
under visible light.
• Complete elimination within 40 minutes under visible light
irradiation, following pseudo-first-order kinetics.
•Green synthesized Co-MOF-based/GCN composite activated
peroxymonosulfate removed antidepressant venlafaxine.
• Achieved 100% removal within 120 minutes with 51% mineralization.
•Au/GCN plasmonic hybrid nanocomposite removed mono-nitrophenols.
• Degraded 99% of nitrophenol, 97% of nitrophenol, and 98% of 2nitrophenol.
• Demonstrated high stability over ten cycles.
•Bi2S/GCN nanosheets effectively removed Cr(VI) and reactive yellow dye
from wastewater.
• Achieved 97% reduction in Cr(VI) within 180 minutes and 94% dye
removal in 120 minutes.
• Enhanced removal attributed to lowered bandgap and improved
charge transfer and separation.
Burdan devam
FOCUS ON WASTE AND BIO-DERIVED
MATERIALS
•
Utilization of biomass or waste for synthesizing green
nanomaterials is a crucial approach.
•
This method involves using abundantly available biomass
or waste, improving sustainability.
•
Biomass-based photocatalyst preparation utilizes various
carbonaceous materials:
•
Activated carbon
•
Carbon dots
•
Graphene
•
Fullerene
•
Incorporating carbon into GCN-based composites
enhances:
•
Photostability
•
Photoactivity
•
Synergistic effects lead to:
•
Increased surface area
•
More active sites
•
Narrowed bandgap
•
Improved surface charge utilization
FOCUS ON WASTE AND BIO-DERIVED
MATERIALS
•
Activated carbon: widely used adsorbent and catalyst support
•
Large surface area and porosity
•
Low cost, easy availability, sustainability
•
Preparation of GCN-assisted activated carbon by Chen et al.
•
Used melamine and activated carbon via pyrolysis
•
Phenol degradation complete within 160 minutes
•
Higher surface area improves adsorption of organic
pollutants
•
Biochar-supported GCN for wastewater treatment
•
Biochar offers advantages as a support for
photocatalysts
•
Porous biochar/GCN used for formaldehyde
remediation
• Prepared using wood-derived bleached kraft
pulp and melamine
• Higher visible light absorption due to biochar
incorporation
• 84.6% formaldehyde removal reported using
250 W high-pressure mercury lamp
•
Incorporation of biochar/GCN with glycine and arginine as
carbon sources can remove orange G and Cr(VI)
FOCUS ON WASTE AND BIO-DERIVED
MATERIALS
•
Pi et al. (2015) developed a GCN-modified biochar to remove MB
•
•
•
Lin et al. prepared modified biochar-based supramolecular self-assembled GCN to remove
phenanthrene
•
•
•
•
85.3% atrazine removal within 260 minutes
Coating of GCN on biochar-ZnO improves visible light activity, increases separation efficiency
Biochar/GCN prepared using waste Camellia oleifera shells and melamine
•
•
Enteromorpha biochar supplies electron-withdrawing groups, π-π interaction minimizes electronhole pair recombination
Core-shell P-laden biochar/ZnO/CN prepared using rice straw and melamine
•
•
•
Modified biochar prepared using KOH and sunflower straw powder as carbon source
Supramolecular self-assembly with melamine and cyanuric acid
Photocatalytic studies: 76.27% phenanthrene removal under visible light, reusability up to four
cycles
π-π interacted biochar/GCN: 90% tetracycline removal within 1 hour
•
•
Carbonization of chestnut leaf biomass, followed by thermal polycondensation of melamine at
520°C
Photocatalytic studies: 91% MB removal due to higher biochar content
Hexavalent chromium ion completely removed by adsorption-combined photocatalysis
Sun et al. (2020) reported GCN/ferrite/biochar hybrid photocatalyst using bamboo fibre as
carbon source
•
96.7% MB removal in 120 minutes, attributed to low graphitization of biochar
FOCUS ON WASTE AND BIO-DERIVED
MATERIALS
•
Zhu et al. (2020) prepared Ce-C@GCN using Alternanthera philoxeroides
Griseb. biochar
•
•
•
Wen et al. (2020) dispersed GCN nanosheets on rice-husk-derived carbon
•
•
•
•
In situ carbon doping increased surface area to 150 m2/g
Zhao et al. prepared C-doped GCN/WO3 using cellulose
•
•
•
•
Wide pore distribution, high ordered degree range, greater mechanical strength
96.2% methyl orange removal, decreasing to 78.2% after fifth cycle
Panneri et al.: 95% tetracycline removal in 90 minutes with spray granulated
GCN nanosheets
•
•
Increased catalyst surface area from 7.7 to 17 m2/g
Dangling C-C bond defects inhibit electron-hole pair recombination
98% methylene blue removal in 4.5 hours with 5 W LED lamp
Wu et al. used wood as carbon source to prepare GCN@C
•
•
•
Enhanced active sites and electron-hole separation efficiency
96% removal of 2-mercaptobenzothiazole with visible light irradiation
Porous structure, GCN surface area of 57 m2/g
Narrower bandgap, improved light absorption, faster interfacial charge transfer
Effective tetracycline elimination
Bin He proposed one-pot construction of carbon/GCN using chitin as carbon
source
•
•
•
93.7% removal of rhodamine B within 3 hours of visible light irradiation
Reduced bandgap from 2.7 to 2.5 eV, stronger visible light absorption
Chitin alters GCN microstructure, interaction with urea leads to higher surface
area
Nanotechnology in Cancer Diagnosis and Treatment
CHAPTER 1
CHAPTER 9
NIR fluorescence emission
Raman spectroscopy/SERS
based immunoassays for cancer
diagnostics
bioimaging
Biomarkers
• Tumor markers and their significance:
• Tumor cells can either obstruct or produce biochemical substances known as tumor markers.
• Tumor markers can be found intracellularly in tissues or in bodily fluids like serum, urine, cerebrospinal fluid,
and saliva.
• Key tumor markers for oral/mouth cancer:
• Oncogenes (e.g., C-myc, C-FOS, C-jun) and tumor suppressor genes (e.g., p53, p16).
• Other markers include cytokines, interleukin, growth factors, matrix-degrading proteinases, hypoxia markers,
epithelial-mesenchymal transition markers, cytokeratins, microRNA molecules, and hypermethylation of
cancer-related genes.
• Role of saliva in tumor marker detection:
• Saliva was traditionally not examined for tumor markers related to oral cancer.
• Technological advancements have led to saliva becoming an important agent for diagnosis.
• Nanotechnology for tumor marker analysis:
• Nanodevices are being developed to analyze tumor markers in saliva, aiding in early detection.
• Nanotechnology enables the detection of biomarkers that may not be visible through conventional imaging
techniques.
• Nanoparticle-based contrast agents improve clinical imaging techniques like CT and MRI, enhancing diagnosis
Spherical Nucleic Acids: Synthesis and Properties
Introduction to Spherical Nucleic Acids (SNAs):
SNAs are three-dimensional conjugates comprising densely
functionalized nucleic acids attached to the surface of
nanoparticles.
The core of SNAs serves dual purposes: imparting novel chemical
and physical properties and acting as a scaffold for organizing
oligonucleotides.
Properties of SNAs:
The nucleic acid shell of SNAs provides functional properties,
including high cellular uptake, resistance to enzymatic
degradation, and low cytotoxicity and immunogenicity.
SNAs exhibit significantly higher binding constants compared to
linear nucleic acids of the same sequence.
Structural Modularity and Biocompatibility:
SNAs are highly modular structures, allowing customization of
core composition, core size, nucleic acid class, and sequence for
specific applications.
Due to their modularity and biocompatibility, SNAs show
promise for gene detection and regulation in live cells.
The Nanoflare: A Platform for Gene Detection
and Regulation in Live Cells
Therapeutic Applications:
SNAs can be delivered intravenously or topically without toxicity or immunogenicity.
They efficiently enter most cells and can regulate the expression of targeted genes.
SNAs have shown the ability to cross the blood-brain and blood-tumor barriers.
Nanoflare Architecture:
The nanoflare is an SNA-gold nanoparticle conjugate functionalized with ssDNA or DNA/LNA
hybrid sequences.
These sequences, referred to as recognition or antisense strands, are complementary to genes
of interest.
A short internal complementary strand with a terminal fluorophore is hybridized onto the
antisense strand.
Principle of Nanoflare Operation:
In the presence of target mRNA complementary to the antisense sequence, a longer, more
stable duplex forms, displacing the shorter flare strand.
Displacement of the fluorophore results in a fluorescence signal proportional to the
concentration of the target transcripts.
Advantages of Nanoflares:
Nanoflares exhibit high sensitivity and specificity in detecting polynucleotide targets.
They can distinguish complementary targets from those with single nucleotide polymorphisms
(SNPs).
Nanoflares enter live cells and detect mRNA expression without significant disruption of cellular
homeostasis.
Unique Features of SNAs:
SNAs enable nanoflares to achieve sensitive and specific detection, surpassing other RNA
detection assays like fluorescent in situ hybridization (FISH) or molecular beacons.
Enhanced binding thermodynamics and selectivity of complement hybridization contribute to
the effectiveness of nanoflares.
Detection of Intracellular Oncogene
• Nanoflare was introduced in 2007 for mRNA detection in living cells.
• It allows detection of intracellular mRNA targets with single-cell resolution
without perturbing cell function.
• This surpasses conventional mRNA quantification techniques like RT-PCR.
• Nanoflares enable cell profiling based on genetic content while preserving
cell viability.
• They have been commercialized by EMD Millipore under the trade name
SmartFlare™.
• Currently, there are over 1700 genetically unique versions available in more
than 230 countries.
Fluorescence Response to Target Oligonucleotides
in Extracellular Conditions
• Nanoflares were designed to detect oncogenes in a breast cancer cell model.
• A specific nanoflare targeting survivin, an anti-apoptotic gene upregulated in various
cancer types, was created.
• Before cell application, nanoflares underwent testing in extracellular conditions with
synthetic DNA targets.
• Testing confirmed the sequence specificity of releasing the fluorophore-labeled DNA
flare strands upon target recognition and binding.
• The Cy5 fluorescence of survivin nanoflares increased 3.8-fold upon incubation with
target DNA.
• No change in fluorescence signal occurred in the presence of a noncomplementary DNA
strand.
• These results demonstrate the efficient signaling of target oligonucleotides by nanoflares
in a sequence-specific manner.
• This capability is crucial for using nanoflares as intracellular mRNA detection probes.
Confocal Measurement of Survivin and Actin Gene
Expression in Live Cells
• Multiplexed nanoflares were introduced to HeLa cells, known for containing high
levels of both actin and survivin.
• HeLa cells were pre-treated with either actin siRNA or survivin siRNA to
manipulate the expression levels of actin and survivin mRNA.
• One set of cells exhibited high survivin mRNA and low actin mRNA levels, while
the other set displayed the opposite.
• Knocking down survivin expression using survivin-targeted siRNA resulted in
decreased Cy3 fluorescence, indicating a decrease in survivin expression.
• The Cy5 fluorescence for actin remained constant in this scenario.
• Treating cells with actin-targeted siRNA and multiplexed nanoflares led to a
decrease in Cy5 fluorescence, suggesting reduced actin expression.
• However, there was no significant change observed in the Cy3 survivin channel.
• These results demonstrate that multiplexed nanoflares can enter live cells and
release two different types of flares with high specificity.
• The fluorescence intensity changes in cells treated with multiplexed nanoflares
corresponded to intracellular gene expression levels, as observed through
confocal microscopy.
Detection and Isolation of Live Circulating Tumor
Cells from Whole Blood
• Nanoflares, with their high cellular uptake and resistance to nuclease
degradation, are ideal for detecting and isolating circulating tumor cells (CTCs).
• Traditional methods for detecting CTCs rely on recognizing specific cell surface
proteins like EpCAM, making them ineffective for cell populations with low levels
of such proteins.
• These methods also struggle to distinguish single-cell genetic profiles among
heterogeneous cancer cell populations, limiting their ability to predict metastatic
potential accurately.
• Nanoflares overcome these challenges by targeting markers of epithelial-tomesenchymal transition (EMT), a critical process in cancer metastasis.
• They are utilized for capturing live circulating breast cancer cells, offering a
unique opportunity to isolate cancer stem cells based on genetic markers.
• This approach has the potential to enhance cancer diagnosis and prognosis by
providing insights into the metastatic potential of cancer cells.
Nanoflares Targeting Markers of the Epithelial-toMesenchymal Transition
• Vimentin, an intermediate filament protein, and fibronectin, an
extracellular matrix protein, are commonly expressed in cancerous cells
undergoing the epithelial-to-mesenchymal transition (EMT).
• Nanoflares were designed to target these two oncogenes and tested in a
model metastatic breast cancer cell line, MDA-MB-231, using analytical
flow cytometry.
• Healthy epithelial mammary cells (HMLE) were used as a control.
• Low fluorescence was observed in HMLE cells treated with the
noncomplementary control, vimentin, and fibronectin nanoflares.
• In contrast, MDA-MB-231 cells treated with fibronectin nanoflares
exhibited 6 times higher fluorescence, while those treated with vimentin
nanoflares showed 8 times higher fluorescence compared to the
noncomplementary control-treated cells.
Recovery Yield of Model Circulating Tumor Cells
Isolated from Whole Blood
•
Vimentin and fibronectin nanoflares were able to distinguish epithelial cells from metastatic cancer
cells effectively.
•
Circulating tumor cells were identified and isolated using a combination of mCherry cDNA expression
in MDA-MB-231 cells and treatment with vimentin, fibronectin, or noncomplementary control
nanoflares.
•
Red blood cells and peripheral blood mononuclear cells were depleted from human whole blood
samples, and the remaining cells were analyzed by flow cytometry for mCherry and Cy5 nanoflare
fluorescence.
•
Over 99% of cells showing high mCherry fluorescence also exhibited a strong nanoflare fluorescence
signal when treated with vimentin or fibronectin nanoflares.
•
Vimentin and fibronectin nanoflares provided a significant enhancement in fluorescence compared
to the noncomplementary control.
•
On average, nanoflare treatment yielded a recovery rate of approximately 68 ± 14% of the spiked
mCherry MDA-MB-231 cells.
•
Nanoflares were capable of detecting as few as 100 mCherry MDA-MB-231 cells in whole blood
samples.
•
These results demonstrate the potential of nanoflares to assess metastatic potential and track
therapeutic efficacy in cancer patients on an individual basis.
Nanodevices
• Importance of AuNPs in Surface-Enhanced Raman Spectroscopy (SERS):
• The properties of AuNPs, including size, shape, surface, and agglomeration state, greatly influence their performance.
• SERS is a versatile technology applicable for clinical medical diagnostics and single-cell studies, providing insights into
molecular composition and structure of living tissues.
• Advantages of Using AuNPs for Oral/Mouth Cancer Diagnosis:
• AuNPs offer simplicity, minimal invasiveness, and increased contrast for diagnosis.
• They are non-toxic and do not exhibit photo-bleaching or blinking, unlike many other fluorophores.
• However, limitations include less active optical signal compared to quantum dots (QDs) and concerns regarding
biocompatibility, tumor targeting efficacy, and toxicity.
• Nanoscale Devices for Cancer Diagnosis:
• Nanotechnology-driven micro/nanodevices, such as nanoscale cantilevers, hold promise for real-time, convenient, and costeffective cancer management.
• Nanoscale cantilevers act as mechanical sensing apparatus, detecting alterations in biomolecule binding.
• Nanopores facilitate efficient DNA sequencing, with recent advancements in magnetic nanopore techniques for isolating
specific extracellular vesicles.
• Nanoshells serve as contrast agents in medical imaging and can distinguish proteins indicative of oral/mouth cancer.
• Gold nanoshells have potential for cancer detection and treatment using near-infrared light, particularly in tumors and
metastasis in solid tumors, including oral/mouth cancer.
Additional slides to this chapter
For 3th April Lecture
Microfluidics for early-stage
cancer detection
•
Fabrication of microfluidic biosensors
•
Microfluidic biosensor development benefits from various fabrication techniques.
•
Laminate manufacturing method is a common and cost-effective approach for microfluidic channel preparation.
•
The method involves stacking independently prepared layers with specific features to form a complete device.
•
A simplest layered microfluidic device consists of a top layer containing inlets and outlets, a patterned flow layer,
and a bottom layer.
•
However, this method has limitations in microchannel width, typically ranging from 50 to 200 μm.
•
Molding techniques, including replica molding, injection molding, and hot embossing, enable the preparation of
more precise and complex microfluidic devices.
•
Replica molding, also known as soft lithography, is widely used for microfluidic device fabrication.
•
It involves preparing a photomask with the desired microfluidic design, transferring the design onto a polymercoated silicon or glass wafer, and generating a replica mold.
•
The mold is then used to create patterned polymer layers, which are peeled and attached to a clean surface to
form a complete microfluidic device.
•
Recent advancements in 3D printing and nanofabrication techniques have improved fabrication precision,
allowing for the generation of nanofluidic channels.
•
However, these methods require specialized training, sophisticated instrumentation, and are associated with
higher expenses, multistep processing, and lower throughput.
Size-based separation of circulating tumor cells in
microfluidics
•
Various microfluidic assay techniques have been developed for blood-based cancer
biomarker analysis, showing potential for point-of-care liquid biopsy.
•
Microfluidic techniques enable cellular and subcellular biomarker analysis from patient
blood samples.
•
Label-free isolation of circulating tumor cells (CTCs) from blood samples is facilitated by
microfluidic approaches.
•
One common principle for microfluidic size-based separation of CTCs involves spatially
distributed micro-nano structures within a capture domain, selectively retaining larger CTCs
while removing smaller biomolecules
•
Another label-free method uses the migration pattern of particles in different streamlines
within specially designed microfluidic compartments, such as circular microfluidic channels
•
In their recent study, Zhou et al. developed a novel microfluidic technique for label-free
isolation and recovery of single CTCs or CTC clumps from complex biological fluids,
minimizing manual handling steps and demonstrating the viability of recovered CTCs.
•
This method utilizes a purpose-built microfluidic channel network comprising upstream
microfluidic conduits for cell separation and a cell trapping domain with arrays of
microchambers for capturing CTCs.
Microfluidic immune-affinity separation of
circulating tumor cells
• The identification of cell surface protein biomarkers on circulating tumor cells (CTCs) has led to the development of
immunoaffinity-based isolation techniques.
• EPCAM-The epithelial cell adhesion molecule - is the most widely used biomarker for CTC analysis, while other biomarkers like
HER2 protein expression are also utilized in microfluidic assay techniques.
• Microfluidic platforms functionalized with antibodies specific to CTC surface biomarkers enable the isolation of target cells from
patient samples.
• Micropillars functionalized with anti-HER2 antibodies facilitate the capture of CTCs, with the unique geometry increasing capture
efficiency Surface modification with nanowires enhances CTC capture and selective release from microfluidic domains, allowing for
target purification and downstream molecular analysis Labeling of antibody-tagged magnetic beads on CTCs and subsequent
retrieval within microfluidic domains is another common approach for cancer cell isolation Integrated microfluidic techniques with
atomic force microscopy (AFM) enable simultaneous isolation and characterization of CTCs based on their physical properties, such
as elasticity and adhesiveness.
• Microfluidic coulter counters combine immunoaffinity-based purification with resistive pulse sensing for direct detection and
counting of CTCs from patient blood samples.
Microfluidic immune-affinity separation of
circulating tumor cells
• DNA structures attached with aptamers are utilized for high-efficiency CTC capture and selective
release, improving isolation specificity and sensitivity.
• A double-mode microfluidic chip combines immunomagnetic and size exclusion strategies for CTC
isolation, although recovery rates may be limited.
• 3D printed microfluidic platforms offer an alternative to traditional cleanroom-based fabrication
methods, enabling efficient CTC capture from complex sample fluids.
• Highly sensitive microfluidic techniques aim to analyze larger sample volumes directly from
patient blood, potentially providing more accurate cancer status assessments.
• Electrochemical readout systems offer an alternative to fluorescence-based detection schemes
for CTC analysis, providing high-efficiency immunomagnetic isolation and detection.
• Microfluidic sensors modified with conducting polymers enable the separation of various types of
CTCs, offering potential applications in regular clinical screening.
• Targeting multiple biomarkers within microfluidic assays may allow for the isolation of multiple
subpopulations of CTCs present in the same blood sample, overcoming heterogeneity in
biomarker expression levels.
Microfluidic biosensors for cancer protein
detection
•
Protein biomarkers circulating in blood provide a source of liquid biopsy
for cancer diagnosis and understanding disease progression
mechanisms.
•
Clinical thresholds for circulating protein biomarkers are typically in the
femtomolar to picomolar range, making conventional techniques like
western blot insufficient for routine pathology laboratories.
•
Microfluidic approaches have been developed for ultrasensitive and
specific isolation and detection of cancer protein biomarkers in patient
blood samples.
•
In a typical microfluidic immunoassay for circulating protein biomarker
analysis, bottom surfaces of microfluidic domains are modified with
immobilized capture antibodies to isolate target protein biomarkers.
•
This antibody functionalization, combined with specific microscopic
designs of microfluidic channels, enables rapid diffusion of target
analytes toward the microfluidic capture domain and enhances isolation
of target proteins by antibody-antigen interaction.
•
Goluch et al. developed a single disposable microfluidic chip for single
protein biomarker detection, demonstrating the potential of microfluidic
technology in cancer protein biomarker analysis.
Microfluidic biosensors for cancer exosome
detection
•
Exosomes are small microvesicles secreted by cells, ranging from 30 to
200 nm in size, carrying cellular materials such as nucleic acids,
proteins, and enzymes, making them important tools for cancer
diagnosis and disease management.
•
Microfluidic approaches have been utilized for exosome isolation from
patient samples, where the capture domain is modified with capture
antibodies, and the patient sample is driven through the device for
efficient exosome isolation.
•
Detection post-capture is typically carried out by labeling the isolated
targets with secondary antibodies.
•
Microfluidic chips can be designed with herringbone-patterns to
increase mixing of sample fluid within the microchannel under
hydrodynamic flow conditions, enhancing collision between target
molecules and capture antibody-functionalized surfaces, resulting in
better recovery.
•
Kamari et al. developed a microfluidic platform with high mixing
efficiency within the fluidic conduit using arrays of micropillars,
enhancing collision between target microvesicles in the sample fluid
and antibody-functionalized micropillars.
Microfluidic biosensors for cell-free DNA
(cfDNA)
• Cell-free DNA (cfDNA) released into body fluids from cancer cells carry signatures associated with the disease condition, making them
effective and minimally invasive means for cancer diagnosis and therapy management.
• Extraction of cfDNA is challenging due to the short size of the fragments (approximately 150 bp) and requires multistep workflows, often
resulting in poor yield.
• Microfluidic techniques have significantly contributed to efficient and specific cfDNA isolation from patient samples for molecular analysis.
• Microfluidic chips for cfDNA extraction can be designed with a bed of positively charged microparticles for capturing negatively charged
DNA fragments. cfDNAs are captured on the microparticles and subsequently released for downstream analysis.
• This method can also be extended for the detection of other circulating nucleic acid biomarkers, such as mRNA and miRNA.
• Another microfluidic approach for cfDNA extraction from plasma samples utilizes polymer and salt-induced condensation (psicondensation) of DNA.
• The microfluidic device contains a photoactive polymer layer for generating COOH surface functionality, allowing for the condensation of
neutralized DNA targets onto the negatively charged surface under hydrodynamic flow conditions.
• This method efficiently purifies cfDNAs from complex biological fluids, with a high recovery rate of cfDNA fragments ranging from 100 bp to
700 bp, and even shorter fragments (50 bp) with a recovery efficiency of over 70%.
Nanodiamond-Based Imaging
•
Nanomaterials are extensively studied as carriers for medical imaging agents due
to their high surface area-to-volume ratios, enabling high loading capacities.
•
Efficient carriers can reduce the required dosages of imaging agents, potentially
mitigating toxicity issues commonly associated with these probes in clinical
settings.
•
Nanodiamonds (NDs) are gaining interest in diagnostic communities for their high
per-Gd(III) relaxivity values, surpassing those of clinical and nanoparticle-based
agents.
•
NDs also exhibit photostable fluorescence and can be utilized for targeted imaging,
further enhancing their potential for diagnostic applications.
•
Conjugating Gd(III) to ND surfaces has shown a 12-fold increase in per-Gd(III)
relaxivity, potentially allowing for a significant reduction in required Gd(III)
dosages.
•
NDs embedded in contact lens devices have demonstrated lysozyme-triggered
drug release and improved mechanical properties, indicating their versatility and
potential for medical applications.
Therapeutic Applications of
NPs and Drug Delivery
Therapeutic Applications of Spherical
Nucleic Acids
• Nucleic acid-based therapeutic agents are composed of short oligonucleotide strands capable of
regulating gene expression, offering potential for precision medicine by targeting specific genes
associated with diseases.
• These therapeutics can be categorized into two main types: double-stranded RNA (dsRNA)
molecules that function through the RNA interference (RNAi) pathway and single-stranded DNA
molecules acting as antisense oligonucleotides (ASO).
• Both types interfere with mRNA molecules to silence protein expression, making them promising
for various medical conditions including cancer, hereditary disorders, heart disease, inflammation,
and viral infections.
• The mechanisms of action differ between RNAi-based gene silencing and ASO-based silencing,
each offering unique approaches to modulate gene expression for therapeutic purposes.
Antisense Oligonucleotides (ASOs)
• Antisense oligonucleotides (ASOs) can inhibit protein translation through
two main mechanisms: steric blockade of translation and recruitment of
the endonuclease RNase H.
• In steric blockade, ASOs bind to target mRNA sequences in the cytoplasm,
preventing ribosomal translation of the mRNA (Fig. 1a), thus blocking
protein synthesis.
• Alternatively, ASOs can induce RNase H-dependent cleavage. In this
mechanism, RNase H recognizes and cleaves the RNA strand of an RNADNA heteroduplex formed by binding of the ASO to its target mRNA. This
cleavage releases the intact DNA strand (Fig. 1b), which can then bind to
additional target mRNAs, recruiting RNase H and enhancing the inhibition
of protein translation.
RNA Interference (RNAi) Pathway
Spherical
Nucleic Acids
(SNAs)
•SNAs offer a highly tailorable therapeutic platform due to their
customizable composition to meet specific application needs.
•SNAs can be composed of various oligonucleotides (e.g., DNA,
siRNA, microRNA, PNA, or LNA) and different nanoparticle
cores, including gold (Au), silver (Ag), iron oxide (Fe3O4),
quantum dots (CdSe, CdSe/ZnS), platinum, silica (SiO2), coreshell (Au@SiO2), and liposomes.
•Coreless versions of SNAs also exhibit useful properties,
emphasizing that SNAs' functionality arises from their densely
functionalized and highly oriented nucleic acid shell rather than
the nanoparticle core.
•Hollow SNAs, such as liposomal SNAs, represent a novel metalfree class with potential in gene regulation.
•Liposomal SNAs offer advantages over conventional
liposomes, stabilizing them in the sub-100 nm range and
facilitating surface arrangement of oligonucleotide cargo.
•Advances in SNA development include attaching RNA to DNAbased SNAs via enzymatic ligation to create RNA-DNA hybrid
SNAs, enabling cost-effective gene regulation similar to other
SNAs.
•SNAs can be backfilled with surface passivating molecules like
polyethylene glycol (PEG) or oligoethylene glycol (OEG) to
enhance colloidal stability, prolong circulation time, and reduce
protein adsorption.
SNAs for the Treatment of
Glioblastoma
Multiforme (GBM)
• Bcl2L12-Targeting siRNA SNAs
Theranostic Magnetic Nanostructures
(MNS) for Cancer
• Monodispersity and uniform composition are crucial for the successful theranostic applications of Magnetic
Nanoparticles (MNS) because their magnetic properties depend on size, shape, and composition.
• High saturation magnetization and magnetic susceptibility, along with stability to various pH and salt
concentrations, are essential characteristics for MNS.
• The size of MNS is a key parameter for magnetization, with smaller particles exhibiting surface spin-canting effects
that decrease saturation magnetization.
• MNS should be under the superparamagnetic limit, typically less than 20-30 nm, to avoid surface-canting effects.
• Coating or surface functional moieties are necessary for MNS to improve dispersion, biocompatibility, and
functionalization.
• MNS can be fabricated using top-down (mechanical attrition) or bottom-up (chemical synthesis) approaches, with
chemical synthesis preferred for producing MNS with uniform composition and size.
• Chemical synthesis methods include co-precipitation, microemulsion, thermal decomposition/reduction,
hydrothermal synthesis, and polyol synthesis.
• Among these methods, thermal decomposition/reduction has gained attention due to its ability to control particle
size, shape, and crystal structure with scalability.
• However, additional surface modifications are often required to impart aqueous stability to MNS synthesized using
organic solvents containing hydrophobic stabilizers.
• Metallic MNS
• Ferrite MNS
• Multifunctional MNS
Coating and Functionalization of MNS
• To apply Magnetic Nanoparticles (MNS) in vitro and subsequently in vivo, surface
functionalization is crucial for various reasons:
1. Protection Against Agglomeration: Functionalizing the surface of MNS helps prevent their
aggregation, ensuring their stability and uniform dispersion in solution.
2. Biocompatibility and Chemical Handles for Conjugation: Surface functionalization provides
biocompatibility to MNS and offers chemical handles for the conjugation of drugs and targeting
ligands, facilitating their interaction with biological systems.
3. Limiting Nonspecific Cell Interactions: Coatings can help reduce nonspecific interactions with
cells, tissues, and biomolecules, enhancing the specificity of MNS for their intended targets.
4. Enhancing Pharmacokinetics: Surface functionalization can improve the pharmacokinetics of
MNS, influencing their distribution, metabolism, and clearance in vivo.
• A variety of organic and inorganic coatings have been investigated for MNS, including DMSA, PEG,
dextran, chitosan, liposomes, gold, and silica. These coatings can be applied through different
approaches, such as in situ coating, post-synthesis adsorption, and post-synthesis end grafting.
Poly(Ethylene Glycol) (PEG)
• Various methods have been employed to coat MNS with PEG:
• In Situ Coating: PEG can be coated onto MNS under aqueous conditions, as
demonstrated by Lutz et al., providing a convenient and straightforward approach.
• PEG Grafting: PEG molecules can be chemically grafted onto MNS surfaces through
single-point chemical anchoring using different functional groups, including silanes,
phosphate derivatives, and dopamine. This approach allows for precise control over the
density and distribution of PEG on the MNS surface.
• Ligand Exchange: Ligand exchange with bifunctional PEG, such as dopaminefunctionalized PEG, has been reported. This method enables the efficient conjugation of
PEG to MNS surfaces, enhancing their stability and biocompatibility.
• Nitrodopamine as Chemical Anchor: Nitrodopamine has been proposed as an
ultrastable chemical anchor for MNS, providing robust attachment to the MNS surface.
Coating MNS with bifunctional PEG conjugated with nitrodopamine and carboxylate
terminal groups results in high buffer stability and versatility for further functionalization.
Dextran
Co-precipitation Method: Dextran can be incorporated into the synthesis of Fe3O4 nanoparticles using the co-precipitation method.
This results in the formation of dextran-coated Fe3O4 MNS, where dextran molecules form a protective layer around the iron oxide
core.
Clinical Applications: The incorporation of dextran into Fe3O4 nanoparticles has led to the development of clinically approved
contrast agents such as ferumoxtran-10 (AMI-277) and ferumoxides (AMI-25). These contrast agents have cores of approximately 5
nm but differ in the thickness of the dextran coating, which affects their blood circulation times. Ferumoxtran-10, with a thinner
dextran coating (20–40 nm), has a longer blood circulation time (24 hours) compared to ferumoxides, which have a thicker dextran
coating (80–150 nm) and a shorter circulation time (2 hours).
Cross-linking to Prevent Desorption: Since dextran molecules are adhered nonspecifically to the iron oxide core through hydroxyl
interactions, there is a possibility of desorption over time. To prevent this, dextran polymers can be chemically cross-linked on the
surface of MNS. This cross-linking enhances the stability of the dextran coating and reduces the likelihood of detachment from the
MNS surface.
Clinical Agents: Clinical agents like ferumoxytol and ferucarbotran have been synthesized using dextran-coated MNS. These agents
have been utilized for various biomedical applications, including magnetic resonance imaging (MRI) and targeted drug delivery,
highlighting the importance of dextran-coated MNS in clinical settings.
Silica
Synthesis: Silica coating on MNS is typically achieved by hydrolyzing silica precursors in a basic solution. This
process results in the formation of a uniform and thickness-controllable silica shell around the MNS.
Drug and Fluorescent Molecule Carrier: The silica shell on MNS can serve as a carrier for various molecules,
including anticancer drugs such as paclitaxel and fluorescent molecules like fluorescein isothiocyanate (FITC).
This capability makes silica-coated MNS useful for drug delivery and imaging applications.
Functionalization: Additional functionalities can be imparted to the silica coating to enable targeting and
labeling functionalities. For example, the addition of 3-aminopropyl-triethoxysilane (APS) to the silica
precursors allows for the coating of silica shells with primary amine groups, with controlled thickness. This
enables precise control over the surface chemistry of the MNS.
Multimodal Diagnostic Agents: Silica-coated MNS can be developed as multimodal diagnostic agents by
incorporating various functionalities. For instance, Lu et al. developed fluorescent MNS by reacting APS with
isothiocyanate-functionalized fluorescent dyes. These fluorescent MNS can serve as imaging agents for
multiple modalities.
Clinical Applications: Silica-coated MNS have found clinical applications, such as ferumoxil (AMI-121), which is
an orally ingested T2 contrast agent used for delineating intestinal loops from adjacent tissues and organs. This
demonstrates the translational potential of silica-coated MNS in clinical diagnostics.
Burdan devam
Targeting of MNS to Localized Cancer
Tumors
Passive Targeting of Magnetic Nanostructures (MNS)
in Cancer Therapy
• Enhanced Permeability and Retention (EPR) Effect:
Passive targeting leverages the EPR effect, where
MNS smaller than 200 nm can accumulate in solid
tumor tissues due to compromised vasculature.
This allows MNS to extravasate from circulation into
tumor interstitium, as illustrated in Fig. 7.
• Limitations: Passive targeting is constrained to
specific tumors, as the success of EPR effect varies
based on factors like lymphatic drainage rate,
capillary disorder, and blood flow among different
tumor types. Normal tissue vessels present a
barrier to MNS penetration due to closely packed
endothelial cells.
Active Targeting with Targeting Agents
• Enhanced Specificity: To overcome limitations of passive targeting, MNS can be modified with tumorselective agents for active targeting. These agents bind to unique receptors overexpressed or present on
tumor cells, enhancing MNS internalization and efficacy.
• Targeting Agents: Various molecules, including small organic molecules, peptides, proteins, and antibodies,
have been utilized for active targeting of MNS. Ligand density and molecular organization significantly
influence MNS binding to target cells, impacting treatment outcomes.
• Challenges: Synthesis of targeting agents is complex and costly, posing challenges for scaling up production
and clinical translation. Despite potential benefits, active targeting strategies require careful optimization
and validation.
• Active Targeting with External Magnetic Field
• Magnetic Targeting: External magnetic fields can be employed to accumulate MNS at specific target sites,
offering a unique feature for MNS-based therapies. This approach has shown promise in delivering
therapeutics to tumor cells in preclinical and clinical settings.
• Clinical Applications: Magnetic targeting has been investigated for various tumor models and successfully
implemented in clinical trials, demonstrating its potential for enhancing drug delivery to cancer cells. Further
research is needed to optimize magnetic targeting strategies for widespread clinical use.
Biotherapy: MNS as Carrier for Gene
Therapeutics
• Gene Therapy Overview: Gene therapy utilizes DNA and antisense RNA (siRNA) to modulate gene
expression, offering potential treatments for various diseases by targeting defective genes.
• Enhanced Nucleic Acid Delivery: MNS coupled with nucleic acids improve plasma pharmacokinetics and
cellular uptake, crucial for effective gene therapy. Cationic polymer coatings like polyethylenimine (PEI),
polyamidoamine, or chitosan facilitate conjugation with negatively charged nucleic acids.
• Challenges with Cationic Coatings: While cationic MNS show promise in vitro, their in vivo applicability is
limited due to toxicity and instability in biological environments. Strategies like coating MNS with a
copolymer of PEI, PEG, and chitosan (NP-CP-PEI) have been developed to mitigate toxicity and enhance
stability.
• Enhanced Transfection Efficiency: NP-CP-PEI coatings demonstrate reduced toxicity and improved gene
transfection efficiency in vivo. Addition of targeting ligands like chlorotoxin (CTX) further enhances gene
transfection efficiency, as observed through histology analysis and confocal microscopy.
• Alternative Approaches: Covalent bonding of siRNA to MNS offers an alternative to cationic coatings. Dualpurpose probes, consisting of MNS labeled with Cy5.5 dye and conjugated to siRNA duplexes, enable
noninvasive imaging and targeted siRNA delivery to tumors.
• In Vivo Monitoring and Silencing: Studies demonstrate the ability to monitor targeting and delivery of MNSbased probes in vivo using MRI and optical imaging. Successful silencing of model (e.g., green fluorescent
protein, GFP) and therapeutic genes further validates the potential of MNS in gene therapy
Chemotherapy: MNS as Drug Carrier/Release
Trigger for Chemotherapeutics
•
Chemotherapy primarily involves delivering small molecule drug
formulations to treat diseases.
•
Many drugs lack cell-targeting capabilities, leading to side effects when
absorbed by healthy cells.
•
Theranostic Magnetic Nanostructures (MNS) have gained attention as drug
delivery vehicles due to their success in diagnostic imaging.
•
Coatings on MNS serve as anchor points for coupling drug molecules,
enhancing targeting capabilities, reducing side effects, and enabling higher
drug dosages at diseased tissues.
•
Various drugs, including paclitaxel (PTX), doxorubicin (DOX), and
methotrexate (MTX), have been combined with MNS for cancer
chemotherapy.
•
Therapeutic moieties can be bonded to MNS with cleavable linkages,
encapsulated in the hydrophobic coating, or physically absorbed on the
surface of MNS.
•
An ideal drug delivery vehicle should facilitate efficient drug loading and
controlled drug release, with options for grafting drugs onto the MNS
surface when they have an affinity for the target cell.
Chemotherapy: MNS as Drug Carrier/Release
Trigger for Chemotherapeutics
•
Kohler et al. demonstrated the covalent attachment of methotrexate (MTX)
to the surface of a PEG-coated MNS using a cleavable amide linkage, but
direct conjugation resulted in low drug loading capacity due to limited
functional groups on the MNS surface.
•
Hollow MNS have been utilized to enhance chemotherapeutic efficacy by
increasing drug loading capacity. Sun et al. used porous hollow Fe3O4 MNS
with five times higher cisplatin loading compared to solid Fe3O4 MNS.
Coupled with Herceptin, these cisplatin-loaded hollow nanoparticles
targeted breast cancer SK-BR-3 cells with significantly lower IC50 values.
•
Labheshwar et al. coated oleic acid-coated MNS with a PEO-PPO diblock
copolymer (Pluronic F127), enabling drug loading of doxorubicin (DOX) and
paclitaxel (PTX). MNS loaded with both DOX and PTX in a 1:1 ratio exhibited
highly synergistic antiproliferative activity in breast cancer cells compared
to MNS loaded with only one drug.
•
Thermal energy from MNS has been used as an external trigger for
controlled drug release. Thomas et al. loaded mesoporous silica
nanoparticles with DOX and Zn0.4Fe0.6Fe2O4 MNS, capping the pores with
cucurbit[6]uril as a heat-labile molecular valve. Controlled drug release was
achieved under an external RF field, resulting in significantly increased
breast cancer cell death.
•
MNS coated with thermally responsive agents such as hydrogels,
thermosensitive polymers, and lipids have been explored for temperaturetriggered drug release. Poly(N-isopropylacrylamide)-encapsulated Fe3O4
MNS loaded with DOX demonstrated enhanced drug release under RF field
activation, leading to increased cell death in HeLa cell lines compared to
controls without RF field exposure.
Nanodiamond-Based
Chemotherapy
and Imaging
3th April
Nanodiamond Drug
Delivery
• Nanodiamonds (NDs) offer unique properties for cancer
nanomedicine.
• HPHT NDs are biocompatible and exhibit remarkable
photostability, making them suitable for cellular imaging.
• Detonation NDs have electrostatic properties conducive to drug
binding, allowing for versatile drug delivery applications.
• ND-drug agents, such as ND-anthracycline complexes, show
promise in overcoming drug resistance in cancer therapy.
• NDX, a scalable ND-anthracycline agent, demonstrates excellent
tolerability and enhanced efficacy in preclinical studies.
• ND-based drug delivery systems have the potential to improve
chemotherapeutic tolerance and efficacy, offering promising
solutions for cancer treatment.
Liposome-Encapsulated Nanodiamonds for
Targeted Triple-Negative Breast Cancer Treatment
• Initial validation of NDX systemic administration
demonstrated promising efficacy against drugresistant breast and liver tumors.
• Improved drug tolerance and therapeutic efficacy,
even at lethal dosages, laid the groundwork for
further development of NDX for clinical use.
• A recent study replaced Dox with Epi in the NDX
complex and targeted MDA-MB-231 triple-negative
breast cancer (TNBC) with EGFR antibodyfunctionalized liposomes encapsulating ND-Epi
complexes.
• NDLPs represent an actively targeted variation of
ND-anthracycline complexes, leveraging enhanced
drug loading on ND surface and improved
intratumoral drug retention.
Nanodiamond-Based Glioblastoma Therapy
•
Blood-brain barrier (BBB) poses a challenge for glioblastoma therapy as
therapeutic agents struggle to traverse it.
•
Off-target toxicity in the central nervous system (CNS) is a major
concern due to irreversible damage to non-regenerating neurons.
•
Localizing drug release to tumor-containing regions is crucial to
minimize off-target effects.
•
Convection-enhanced delivery (CED) of NDX directly into brain tumors
showed improved tumor localization and treatment efficacy.
•
Preclinical studies in rodent models demonstrated enhanced cancer cell
death and improved drug retention with NDX administration compared
to free Dox.
•
NDX administration via CED resulted in healthy brain tissue in the
surrounding areas, indicating minimized off-target toxicity compared to
free Dox administration.
•
NDX shows potential for confining drug delivery to tumor-containing
regions of the brain, thereby improving the tolerance of CED Dox
injection.
Localized Nanodiamond Drug Delivery
• A-diamond-embedded chitosan nanogels was used to trigger
timolol release using lysozyme.
• Timolol, a glaucoma drug, is often administered via eyedrops, but
patient compliance is a challenge.
• ND nanogels embedded within contact lenses were compared with
drug-imprinted and drug-soaked lenses.
• Drug-imprinted and soaked lenses showed burst release, releasing
most of the timolol within hours.
• ND-based lenses released timolol gradually upon exposure to
lysozyme, potentially improving drug storage and release.
• Lysozyme in tears triggers localized drug release after lens use in the
eye, enhancing drug delivery.
• ND-water interactions maintain water content in the lenses, crucial
for proper lysozyme access and wear comfort.
• Mechanical robustness of the lenses was improved with ND-based
composite formation, indicated by increased Young's Modulus
Assessment of Nanodiamond Safety
• Biocompatibility assays XTT-Cell Proliferation Kit II- cell proliferation
assay to examine cell metabolism,
• lactate dehydrogenase (LDH) cytotoxicity assay, and caspase 3/7
apoptotic induction assay
Mitochondrial dysfunction and cancer: modulation
by palladium α-Lipoic acid complex
• Repairs DNA damage resulting from radiation.
• Scavenges free radicals and lowers lipid
peroxidation.
• Increases the levels of glutathione and glutathione
peroxidase(GPx).
• Increases the levels of manganese superoxide
dismutase, and catalase.
• Enhances the Krebs cycle enzymes: isocitrate
dehydrogenase, α-ketoglutarate dehydrogenase,
succinate dehydrogenase, and malate
dehydrogenase. Enhances mitochondrial
respiratory enzymes
• Promotes cell death in a variety of cancer cell lines such as
skin melanoma, hu-man (SKMel-5); liver, hepatocellular
carcinoma, human (Hep G2); lung, ma-lignant melanoma,
human (malme-3M); mammary gland, ductal
carcinoma,human (MDA-MB 435); prostate, left
supraclavicular lymph node carcinoma, human (LNCaP);
colon, colorectal adenocarcinoma, human (HT-29); human
brain, glioblastoma; astrocytoma (U87); and glioblastoma
(U251MG).
•
Acts as a prophylactic for neuronal protection from transient
ischemic attack.
• Acts as a prophylactic for protection from radiation.
• Exhibits unique electronic properties corresponding to diode
or tunnel diode behavior
Nanotheranostics
• Combination therapeutic and imaging functions in a nanocarrier.
• Actively targeted or stimuli-responsive nanoparticles in theranostics are termed "smart
delivery" or "activatable" systems.
• These nanoparticles are shielded during systemic circulation to minimize off-target
effects and background noise.
• In the tumor region, the drug and imaging agent are released or activated.
• Nanotechnology enables integration of multiple properties in a single platform, including
passive targeting, target-triggered activatable release, multimodal imaging, and therapy
capabilities.
• Technological advances in nanotheranostic systems impact drug development and
treatment planning at the patient bedside.
• Real-time imaging of drug accumulation in the tumor region can optimize drug
formulation during research and development and predict patient response to drug
doses.
Lipoprotein Theranostics
• Lipoproteins consist of a hydrophobic lipid core and an outer shell of
phospholipids and amphipathic apolipoproteins.
• They offer advantages for drug delivery:
• They evade recognition by the immune system and clearance by RES due to their
endogenous nature.
• Their long circulation time in the bloodstream enables systemic drug delivery without
requiring PEG coating for stability.
• Lipoproteins facilitate stable delivery of hydrophobic bioactive compounds, allowing various
loading approaches.
• Interaction with apolipoproteins ensures consistent particle composition and size
distribution, enabling targeted delivery.
• Lipoproteins have been used to deliver various chemotherapeutics and other
agents.
• Many comprehensive reviews are available on their applications in drug delivery.
Synthetic High-Density Lipoprotein-Like
Nanoparticles as Cancer Therapy