Minh, Skipper, Alan
What are Nanoshells?
Nanoshells are very small beads with a dielectric core such as silica surrounded by an
ultra-thin metal shell, often composed of gold for biomedical applications (Hirsch). Nanoshells
typically range between 5 to 30 nanometers (Hirsch). By carefully engineering the size of both
components, scientists can produce nanoshells that absorb or scatter light across a wide spectrum
– from ultraviolet range to near infrared. The later is particularly useful in biological
environments; 800-1300 nanometers is considered the ‘water window’, a region of high
physiological transmissivity, that is optimal for imaging and sensing. These wavelengths can
easily penetrate several centimeters of tissue (Alivisatos 67).
Making Nanoshells:
Nanoshells are developed using an approach
that combines techniques of molecular selfassembly with the reduction chemistry of metal
colloid synthesis. Silica nanoparticles are grown via
the Stober method as the dielectric cores.
Organosilane molecules (3Aminopropyltriethoxysilane) are then adsorbed
onto these nanoparticles. These molecules bond to
the surface of the silica nanoparticles, extending
their amine groups outward. After isolating the
coated silica particles from residual reactants, a
solution of very small gold particles (1–2 nm in
diameter) is added. The gold particles bond
covalently to the organosilane linkage molecules
via the amine group (Oldenburg et al.). This
scattered layer of gold particles serves as nucleation
sites for further reduction of gold onto the silica
core by reduction of gold in a chloroauric acid
solution; as more gold is reduced the surface coating
grows into a complete shell (Hirsch). Figure 1
illustrates the growth of the gold particles on the
silica nanoparticle surface, which is typically
completed within a few seconds.
Figure 1: This is an electron micrograph that illustrates the
process of the reduction reaction that increases the coverage
of gold particles. This is a 120 nm diameter silica core
decorated with about 2000 gold nanoparticles in Fig. 1a.
(Image retrieved from Oldenburg et al.)
Medical Applications of Nanoshells:
With regards to medical treatment, nanoshells have particular use in combating cancerous tumors
and are currently in development for treatment in humans. As of right now, the methods using
Minh, Skipper, Alan
nanoshells have been prototypically tested only in mice, though with extremely favorable results.
Though the environment will be different, the methods will remain constant: using the
nanoshells’ special optical properties, the cancerous tumors will be targeted with some form of
near-infared (NIR) light which will be converted through the nanoshell intermediate into heat
and energy, used to dissipate and destroy the cancerous tissue.
Absorbing Radiation in Nanoshells:
The reason that nanoshells are favorable in transforming light energy into weaponized heat is due
to its primary structure; namely, the metal colloid shell, most often times gold. Metals are far
superior to other elements in manipulating energy due to the way that they handle their electrons.
With normal elements like carbon and hydrogen, the electrons they carry are usually restrained
in bonds to certain locales and moderately rigid. With metals however, their electrons are free to
roam amongst each other, creating a sea of electrons in a manner. Therefore, the electrons in
metals are more easily excitable to a higher energy state. As the light emitted strikes the
electrons on the nanoshell and causes them to become excited, the electrons will oscillate
instantly and convert the light energy into thermal motion in moving about and returning to their
base energy state. The light that causes the electrons to excite is specific to the size and
interspacing of the gold nanoshell, similar to how a spring or wave resonates at a specific
oscillation frequency. This phenomenon in nanoshells is defined as surface plasmon resonance.
Nanoshells are very effective at converting light to heat; studies have shown that nanoshelltreated tumors have had temperature increases of 37.4 ± 6.6°C on NIR exposure for 4-6 minutes,
which is well above the damage threshold for cells (Hirsch).
Targeting Tumors:
There are two primary ways of eliminating cancerous cells with nanoshells. The first involves
direct contact between the surface of the cell and the nanoshells. In order to make the nanoshells
bind to the surface of the cell, scientists must attach antibodies to the surface of the nanoshell to
recognize and bond to the tumor. When about twenty to thirty of these shells are bonded to the
cell, the scientists will bombard the subject with light for about 4-5 minutes, the electrons will
excite and dissipate enough energy to heat up the environment, in this case the cell and destroy
it. The second alternative is to introduce the nanoshells to a phagocyte in order to engulf them.
The phagocyte will form an inner macrophage to isolate the nanoshells inside and then gets
shipped into the cancer cell as part of routine cellular functions. Inside the cancer cell, the
phagocyte is metabolized and transported back out of the cell, but the nanoshells are not
metabolized and remain inside the tumor cell. Then the same light treatment is administered and
the cell is eliminated from the inside out.
Other Applications:
Nanoshells potential for cancer treatment is an application that gets a lot of publicly, but
there are also other exciting potential applications for nanoshells. One of the exciting
Minh, Skipper, Alan
applications of Nanoshells is the delivery of drug molecules at specific times by attaching them
to a capsule made of a heat-sensitive polymer (Alivisatos 68). The capsule would release its
contents only when gentle heating of the attached nanoshells causes it to deform (Alivisatos 68).
Nanoshells can also be used for immunoassays, which are antibody-antigen interactions to detect
a specific antigen within a complex mixture and is commonly used in the analysis of a blood
specimen (Hirsch). The ELISA test, the most widely used immunoassay, suffers from a few
limitations because it relies on either fluorescence or a colorimetric change in solution and it
requires a lot of filtration and purification that lengthens the time needed to conduct the complete
assay, from 4 to 24 hours (Hirsch). Nanoshells can resolve this problem through a newly
developed immunoassay technique that utilizes antibody conjugated, near infrared resonant
nanoshells, which can be performed in whole blood and results within several minutes (Hirsch).
Nanoshells can also serve as a biomedical optical imaging agent. By designing nanoshells to
scatter rather than absorb light they have the potential for high-resolution in vivo imaging
(Hirsch).
Minh, Skipper, Alan
The core of the model representing the silica dielectric core was modeled using an 80 inch
diameter Styrofoam ball, spray-painted silver not only to distinguish it from the other pieces in
our model but to also model silica’s appearance. The gold colloid bonded around the silica
core is represented by another series of Styrofoam balls, this time one inch in diameter and
spray-painted with gold and yellow color for obvious reasons. The amine bonds between the
gold particles and the dielectric core are modeled using pipe cleaner, this time blue in
appearance to distinguish from the other components of the model.
Minh, Skipper, Alan
References:
Alivisatos, Paul A. “Less Is More in Medicine.” Understanding Nanotechnology (2002): 58-69
Hirsch, et al. “Metal Nanoshells.” Rice University, Department of Bioengineering 34 (2006) pp.
15-22. Web 24 April 2010
---. “Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic
resonance guidance.” Rice University, Department of Bioengineering 23 (2003): 1-6. Web 24
April 2010
Oldenburg, Averitt, Westcott, & Halas. “Nanoengineering of optical resonances.” Chemical
Physics Letters 288 (1998) 243-247. Elsevier. Web 24 April 2010