Richard Fisher
Intro
Sponsers
Supporters
Mission
Dr. Micheal Gottesman (7:30mins)
Introduction to conference
Nanotech is more than just molecular biology at the nanoscale
Nan development of devices
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His work is: Multi-drug eFlUX pumps (8mins)
o How they work and how they create resistance to cancer drugs
o Circumvent the activity of these pumps
 Using nanoparticles to deliver drugs to cells
 Development of nano-imaging
 Combining the two
Construction of nanoparticles for cancer therapy (8:30)
o Chemical Appraoches
 Can circumvent normal paths to attack(get to) cells
Ethics (9mins)
o Environmental caution
o Need for caution
Integrating different areas of nanotechnology and research
Dr. Mark Ratner
Interests: Structure and Function at the nanoscale & theory of fundamental
chemical processes
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 Nanoscale behaviors from metal to biology
nanoelectronics
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Nanoscale (13:30)
o 100 nanometers to 1 nanometer
 Different things along the scale
 Bacteria/virus
 Gold
 Hybrid synthesized gold nanostructures
 C-60’s
- Design scale of nature
- self assembling structures
- size-dependent behaviors
- Moving nanoparticles (15mins)
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Patroleum refinement
- breaking up petroleum particles at a smaller scale = releasing more
octane material from the gas
- Already in use - 40% of US gas
- self-assembly (18mins)
- making utensils that can work at the nanoscale (nanotip- 20:30mins)
- nanotips can write nanowriting
- nanomarking of medicine
- smaller and smaller materials creating smaller and smaller work
- Fabrication techniques
- templates for nanostructures
 Painting on nano-structures
 paint is molecular biological substraints
Fabrication tech
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Molecular Nanorod Regenerative Medicine (25mins)***
o based on self assembly
 naturally binding chemicals/particles
 use natural properties to create nanostructures
o upon injection self assempling “GEL”
 biorecognition code (natural code)
 natural binding results in a certain particles to separate and
form an outer “shell”
o Example of treatment  spinal chord injury
 Destruction of communication systems
 Injection at injury site with proper chemical attraction creates self
assembling reconstruction of communication paths
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Cholesterol Remediation (29mins)
o Lipoprotien cycling
o Decrease LDL
o Increase HDL
 Therapeutics
o synthesize lipid particles
 start with gold nanoparticle
Binds cholesterol
o Use for Therapeutics
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All Based on Self Assembly- directed self assembly
Directed Assembly
Size dependent behavior (33:30)
o Golds behavior changes when it gets to small that it is almost all surface
area
o Size and shape changes properties
o Like bells and sound frequency
Dr. Shuming Nie (42mins)
- Development of probes for intracellular and single molecule imaging
- How does the size of the particle determine its interaction with other molecules
and biological particles
- Semi conductor quantum dots (44mins)
o Size tunable QD
 Different sizes determine different color due to genetic makup
o Composition Tunable
 Outside composition is the same yet inside chemical makup varies
= effective mass
o Strain Tunable
 Changing the surface changes the entire composition
 Changes core
 Change energy band gap
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using opical properties of these nanodots for imaging
o single molecule imaging
problem is the size of the composite on the core (entire particle) (54:30mins)
o creating thinner coating particles
o size dependent interaction between particles and biological molecules
o future hold smaller quantum dot abilities
Dr. Xiaowei Zhuang (1:11mins)
Bioimaging at the Nanoscale
o overall imaging at different levels (1:12mins)***
- Light Microscopy
o Light is not invasive – easy to study a live sample
o Light has many different colors- allows for many different color probes
o Light labeling approaches are uniform
o However light microscopy is limited in how small it can get – not
molecular scale
 Limited by diffraction (limited by lenses)
 Resolution becomes muddy
 some ways to work with diffractions limitations
 been able to localize single particles
o overcoming the light limitation
 reconstruct isolated images to determine center of all molecules
individually
 Stochastic Optical Reconstruction Microscopy
o to image isolated particles need dye that can be imaged with florescent
lights
 found best floraphore
o Super r esolution imaging (1:27:30mins)
 Dynamic resolutions
 Multiprtoien/color activations
o 3D imaging resolution
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 Building imaging through different imaging areas put together
 New quantitative abilities
 Can now measure interactions
resolution based on localizations of precision and density
o GAINED localization accuracy and strategies
o These high scale images of natural biological dynamic interactions in real
time is the main gain
Dr. Milan Mrksich (1:47)
Nanomaterials for the study of cell adhesion
o nanomaterials are interacting with protein layer on top of glass/plastic
materials
o proteins substrates are difficult to adhere to the surface of materials
o Self-assempled Monolayers  alkines, thielanes and gold
 Nanotip writing with sulfer on gold
 Sulfer (or the chemical at the end of the tip is created to
synthesis with the substrate coating of the target materials
(ie sulfer and gold will synthesis)
o These tips are made up of many chemicals that are
now connected to the target material
o **Self assembly – directed interactions
- dynmic cell adhesion (1:55)
o can we create a mutli-interactive monolayers
 electroactive monolayers –that selectively release
 single cell multi-manipulations
 electrochemistry
- made one aspect of the monolayer a electrochemical reaction to detach specific
cells after they have been attached
o breakthrough in the ability to prepare molecular level designs for active
interface between cells and substrates
 got through the problem of dynamic cell interaction altering the
substrates or the molecular makeup
 picture of actual microscope and substrate materials (2:00)
 much previous work was limited in the way they could have two
cells interact
 can now control more precisely what to cells interact/ and
the timescale over which they interact
 fiberblasts – the way in which the turning on of cellular
function is done
o can either turn on and must sstay on or could turn
on can then not needed
 depends on functioning levels
- designing cell surfaces
o chemical dynamics (cool cell picture 2:04)
o shapes
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polymer on biological materials
 light shown through a mask
o places that are hit by light are degraded
 left with a polymer pattern on the surface
 then gel polymer material is poured
over structure and peeled off giving
casts of the original polymer
o then shape surface of cast
with ink substrate controlling
the area which will interact
with a cell and create
monolayers
o controls cellular interaction
area
 How cellular patterns control interaction
o Can develop averages(heat maps) of many cell if
they have the same pattern
 Certain shapes enable better interactions/ anchoring of
contractility
o geometric ques that define the cytoskeleton of the
cell and its state of contractility
 strong convex edges are best localization
points
 can manipulate these convex edges
for dynamic optimization
o stem cell study (2:11)
 can manipulate the future a cell will choose by manipulating its
tendencies
 bone cell/ fat cell
 cell pattern determines fate
 can also manipulate contractility through the manipulation of
cytoskeletal makeup
 but drug manipulation nulls the shape effects
o ready for gene cell arrays
 large similar shaped molecules decreases the noise usually found
in exp.
Carlos Bustamante (2:22)
The cell is a small conductor
- complicated factory made of different localized functions
o energy transfusers
 energy into mechanical force
- virus mechanism (motor)
o target of drug implementation
- precise measurement of virus and cell interaction (dna packaging)
o through the motor processes
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across time – molecular packaging slows at the half way
 higher and higher forces required for molecular packaging
o motor is extremely powerful
 measure internal force of dna on virus
 virus can package incredible amount
of dna ---infection
o can determine the packaging rate of a single phage
 then can force virus motor to attach to a non-hydrolyzable analog
which will force the motor to stall
 more nonhydrolizable ATP results in longer motor stalls
o can determine the nature of the chemical interaction between virus and
substrate
 chemicals determine charge
 chargless DNA can cause a failure in the virus motor
o increase of chargless DNA = increase in motor
failure
 attaching chargless DNA to different parts of the DNA causes
different effects on the virus’ motor ability
 new ways to maximize packaging
o breaking down packaging into subphases
 makes for larger control (control of smaller
and smaller functions)
 modeling different phases of packaging
 (movie animations of new model (2:56)
Mauro Ferrari (3:00)
Individualized Medicine
- The right drug to the right person in the right circumstance
o Nanotechnology to help all aspects
- Bimolecular individualization
o Drugs at the time
o Drug at the right place
o Monitoring the drug effect
- molecularly targeted medicine with nanotechnology participles that carry active
moieties
o drug release
 time delivery – responsive to circumstances
 build nanoscale channels inside of silicon membranes using an
innovative technology  silicon chip fabrication technology –
microelectronics industry
- Directing therapy
o Affective tumor growth therapy
o Heating of nanoparticle for tumor destruction
 Remote activation
- biological distribution
o controlling probability
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 density effects
design prescription
o how low can we individualize therapy
 control degradation rates of individual particles
 quantum dots, nanotubes
personalization at the subatomic level
o written in blood
 real time efficacy monitoring
controlling time profile of release of bioactive agents
o release from intravascular vectors
o release of agents or vectors from implants
Individualizing of optimizing intravascular transport
o Rational design of delivery vectors
o Thru biological barriers via multi-stage systems
monitoring of therapeutics efficacy
Dr. Kathrine Lewis (3:38)
- overview of NIH nanotechnology programs
o The national Nanotechnology Initiative NNI
o NCI alliance cancer institute
 Imaging and early detection
 Multifunctional theraputics
Links to all NIH funding opportunities and current projects
http://www.nih.gov/science/nanotechnology/index.htm
http://www.nih.gov/
Dr. Dennis Buxton (3:55)
- NHLBI programs of excellence in nanotechnology
- leading people in the different programs
- brief snippets of each focus
Gang Bao (4:06)
-PEN
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Cardiovascular Disease
o Diagnosis and treatment
Miochardial healing
Heart transplant
Asthma
Targeted comb copolymers and nanoassemblies
Optimization of targeting procedures
Using quantum dots for florescence imaging
o Labeling of multiple epitopes
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Biodistribution
Hydrocynanines for imaging ROS in Vivo
o Activatable fluorescent catB sensors
o Multiple contrasts in one
invivo delivery
o higher efficient
o individual cell detection
Ralph Weissleder (4:43)
- Nanosensors for molecular application
o Used in devices, nanomaterial development, and clinical treatment
o Bringing these devices and materials to the patient
o Magnetic nanomaterials detection of lymph node metastasis
 Magnetic resonance for metastsis detection
 Increased diagnostic ability
 Diagnostics are done automatically
o Compare new images to database of old images
 Output shows diagnostics
 Can now make diagnostics on small or early stage
malignants
o Target cancer cells
 New technologies to detect more and more specific substances
 Studying blood cell through magnetic device
o NMR
 Look straight through blood to diagnose
 Built a hand held NMR system
 Microcoils, magnet, microfluidics
for blood incubation of cancer cells,
o Oassed over detection coils
for diagnosis
o 4X8CENTIMETERES
o All electronics in one
transceiver
o Single cell detection level
o Labeling of cells through cell
type/shape/other
quialities/level of severity
o development of compound nanomateriales/ substraites for specific
purposes
o Targeted siRNA delivery using multifunctional nanoparticles
o NC’s/ quantum dots that combine targeting and sensing
 Developing different targeting styles/ approaches
Jeff Scholoss (5:10)
- Nanomedicine Roadmap initiative
o Discussion of components of the roadmap
o Moving from the science to the production to the implementation
Wah Chiu (5:21)
- Protein folding materials
o Synthesized protein in the ribosomes
o Interested in the folding and unfolding of protein folding
 Group 2 Chaperonin
 ATP hydrolysis to fold substrates
 dealing with the process of the protein folding within the
chaperonin and the design principles of chaperonin
 want to design chaperonins to fold biolmedical substrates
 develop adaptors for more developed folding
 develop drug nano-cage for drug delivery based on
chaperonin platform
 develop outreach for nanomedicine
 targeted delivery
 Chaeronin & substrate design
 Structures
 Dynamics –single molecule imaging
 Simulations –modeling and design
 Biochemistry – cell biology
 -Protien misfolding in a disease
 understanding the structulral design of the Mm-cpn Chapreronin
 localizings individual particles
 reconstruction high resolution animation
o density diagrams
 Engineering a new chaperonin
 Understanding open and closed states of the Cryo-Em
 Understanding the structural changes in ATP Hydrolysis
 Understanding interaction between two states (closed and
open states) across rings
 Biochemists test the chemistry of the structural changes and
the interactions of the chaperonins during hydrolysis
process
 Protease K experiment
 Identify key residues to keep the subunit together during its
atpase cycle
 The subunit moves almost as a rigid body between the open
and closed conformational states.
 Built in lid is not critical for ATP induced conformational
changes
 ABEL Anti-Brownian Electrokokinetic – Trap for determining
ATP Binding in Chaperonin
 Maximum efficiency for single cell biochemical detection
(6:01)
- Harnessing the power of Nanotechnology for Human Health at the Natioanl
Institutes of Health
- NIH mission
- Translating the research framework to nanotechnology
Martin Philbert (6:15)
- Synthesis and Manufacture
o General overview
o Problem with mode of manufacturing
 High surface areas to volume ratios
 Excellent potential for absorption of unwanted synthetic
materials.catalysts on the surface
 Enhance possibilities for nuisance surface chemistries that alter
biological macromoleculres
 For labile nanoparticles, potential release of contaminatnes into
biological environments
 Use of Green Chemistry will become increasingly important for
sustainable development
o Safe design will vary widely with each development
o Role of conglomeration
 Size and surface area
 Increase exponentially
 Unpredicted effect on internal areas
 Aggregation in situ may lead to formation of microemboli
and local infarction
o Some cells will accumulate and aggregate
nanomaterials
o nanoparticles are invariably heterogeneous
 surface charge
 can penetration and translocation occur
 quantum dots
o translocation to proximal lymph nodes
o Hydrophobicity
 Cell integrity
 Bio-compatibility
 Role of Reticuloendothelial System
o Effects of PEG Weight on dynamis MRI scanning of nanoparticles
 Degradable nanoparticles
 Excellent tumor imaging
o Targeting specific sites
 Sub cellular localization
 Flexible photonic chemistry options
 Ormosils “nanobottles”
 Intracellular 3-D opto-chemical imaging
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o Photodynamic apparoaches
 Nanoparticles can be used to kill resistant cancer cells
 Invivo evaluation of antitumor activity of PDT nanoparticles
o From the lab to the neurological suite
 Staining of a tumor for optical delineation
 Optical tagging of orthotopic tumors
Safe nanomedicines
o Green manufacturing will be prudent
o Choice of chemical in manufacturing is critical
 Nutritional applications
o surface-mediated targeting is feasible
o biodegradable particles will help to optimize