Cancer Therapy

Key Words:
Nanotechnology, nanoshells, gold, dielectric core

Abstract:
In the recent days many people all over the world are affected by cancer.
Cancer is a disease in which there is uncontrolled multiplication and spread within the body
of abnormal forms of body’s own cells. It is major cause’s death in developed nations.
American country people are mainly affected by cancer.

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy,

monoclonal antibody therapy or other methods. The choice of therapy depends upon the
location and grade of the tumor and the stage of the disease, as well as the general state of
the patient. A number of experimental cancer treatments are also under development.

NEWER AND EXPERIMENTAL APPROACHES TO TREAT CANCER

• HAEMATOPOIETIC STEM CELL APPROACHES

• ISOLATED INFUSION APPROACHES
• TARGETED DELIVARY MECHANISMS
• NANOPARTICLES

The noninvasive cancer treatment uses a combination of harmless, near-infrared light and
benign, gold nanoshell to destroy tumors with heat. The treatment does not affect healthy
tissue. Nanoshells are a type of nanoparticles which are used to treat cancer. Metal
nanoshells are a type of composite spherical nanoparticle consisting of a dielectric core
covered by a thin metallic shell which is typically gold.

One of the promising applications concerns the biological field. Research is being
performed to create nanoshells with high absorptions at biologically useful wavelengths
by altering the thickness of the shells. Particularly, the Near Infra Red region, which
corresponds with low absorption by tissue, may be useful.

Introduction:

The branch of medicine concerned with the study, diagnosis, treatment, and
prevention of cancer is oncology. Cancer is a class of diseases in which a group of cells
display uncontrolled growth, invasion, and sometimes metastasis. Cancer may affect
people at all ages, even fetuses, but the risk for most varieties increases with age.

Nearly all cancers are caused by abnormalities in the genetic

material of the transformed cells. These abnormalities may be due to the effects of
carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other
cancer-promoting genetic abnormalities may be randomly acquired through errors in
DNA replication, or are inherited, and thus present in all cells from birth. The heritability
of cancers is usually affected by complex interactions between carcinogens and the host's
genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation,
and microRNAs are increasingly recognized as important. Normal cell proliferate
through definite cell cycle that causes programmed DNA replication.

Nanoparticles are of great scientific interest as they are effectively a bridge between bulk
materials and atomic or molecular structures. A bulk material should have constant
physical properties regardless of its size, but at the nano-scale this is often not the case.

In nanotechnology, a particle is defined as a small object that behaves as a whole unit in

terms of its transport and properties. It is further classified according to size: In terms of
diameter, fine particles cover a range between 100 and 2500 nanometers, while ultrafine
particles, on the other hand, are sized between 1 and 100 nanometers. Similarly to
ultrafine particles, nanoparticles are sized between 1 and 100 nanometers, though the
size limitation can be restricted to two dimensions. Nanoparticles may or may not exhibit
size-related properties that differ significantly from those observed in fine particles or
bulk materials .

Classification of nano particles:

At the small end of the size range, nanoparticles are often referred to as clusters.
Nanospheres(nanoshells), nanorods, nanofibers, and nanocups are just a few of the shapes
that have been grown.

Nanoshell:

A nanoshell is composed of a spherical core of a particular compound surrounded by a

shell of a few nanometers in thickness. The nanoshells collected in the tumors due to the
permeability of the tumor tissue. When intense infrared light was shone on the tumors,
the nanoshells converted the light to heat--enough heat to kill the cancer cells in the
tumors.

Special gold nanoparticles called nanoshells are being investigated for uses in both
imaging and destroying cancerous cells. Nanoshells can be engineered to target cancerous
cells and at the same time designed to interact with specific wavelengths of light.
Depending upon the wavelength of incident light, nanoshells can either scatter or absorb
light, creating applications as both a cancer imaging agent or therapeutic one. Several
research groups have performed successful studies that prove nanoshells can be used to
create high-resolution images of tumors as well as a precise treatment procedure that
research groups have performed successful studies that prove nanoshells can be used to
create high-resolution images of tumors as well as a precise treatment procedure that
causes cell death in tumors. Currently researchers are awaiting FDA approval to begin
clinical testing of these methods.
Gold Nanoshell Design:

Metals are a unique class of materials. One special attribute is the ability of metallic
nanoparticles to strongly interact with electromagnetic waves (light, radio, x-ray, etc.).
When electromagnetic waves, such as light, shine on a metallic nanoparticle, it can start
an interaction known as surface plasmon resonance. In particular, gold and silver both
display very strong surface plasmon resonance effects. Of these two metals, however,
gold is far less dangerous to be used in the body. The use of gold in medicine has been
documented for over 50 years.

So, not only does gold have useful physical properties, but it also has useful chemical
properties that make it better for treating cancer than other potential materials. While the
properties of gold are impressive and obviously important, it is really the structure of
nanoshells that allow for progress in cancer treatment.

Nanoshells can come in many shapes and sizes, but all are composed of a core and a
shell. The core is the interior part and the shell is the material coated around the core. In
the case of a gold nanoshell the core is a ball of silica and the shell is a thin layer of gold.
Gold nanoshells have similar properties to gold nanoparticles (plasmon resonance,
scattering, etc.), but have the added benefit of being tunable to different wavelengths of
light.

Gold nanoshells are also more efficient at converting EM waves to energy than
nanoparticles. This is due to plasmon resonance along both the inner and outer surfaces
of the shell, as opposed to a nanoparticle only having resonance along the outer surface.

Gold Nanoshells Fabrication:

Over the past decade, nanoshells have been created with all sorts of dimensions, shapes,
and sizes. Some look like balls, others resemble rods, and some are even shaped like
eggs. Such particles may look and behave differently, but they are all made in a very
similar way. The general process for fabricating nanoshells is:

1. Grow or obtain a nanoparticle sized dielectric core (such as spheres of silica, but
they could be other similar compounds and different shapes).
2. Chemically treat the surface of the core to make it "sticky" and ready for growing
gold from solution (this allows adding a gold shell to the core).
3. Grow gold "seed particles" on the surface of the core and then plate gold on top
until a complete layer has formed (the seed particles will allow more gold to be
coated on top to form a shell).
While some of the more complicated nanoshell structures require additional steps for
fabrication, almost all nanoshells share the above process. The process is very similar to
creating paper-Mache globes, where a balloon represents the core, and the paper strips
represent the gold. It is easy to blow up the balloon (creating the core of a nanoshell), but
not easy to start adding paper at first. However, once a few strips of paper have been
successfully stuck to the balloon, it becomes easier and easier to add more paper. There
are many different factors to control and check before nanoshells can be efficiently used,
including controlling shell thickness and adding surface coatings. Changing the shell
thickness changes optical properties of the nanoshells. Adding surface coatings allows the
nanoshells to target and interact with different things in the body.

After creating the nanoparticle, treat the nanoshells for a length of time with special
chemicals to etch the shell size down in thickness. By doing this, the surface of the
nanoshell is made rough. By thinning and roughening the surface of the nanoshell, the
absorbed wavelength of light is changed from visible wavelengths into the near infrared,
a spectrum of light which passes through the human body without causing any harm.
Controlling which wavelength of light is best absorbed is one of the most important
features of nanoshells.

Gold Nanoshell Immunotargeting:

The gold nanoshells have been prepared; they need to find the cancer cells to connect to.
Billions of gold nanoshells are injected into the blood stream and begin to travel through
the body's blood stream. Gold nanoshells are seen as foreign objects in the blood and will
be targeted for removal. To help gold nanoshells navigate the blood stream, nanoshells
are coated with poly ethylene glycol, or PEG for short, which allows them to circulate the
blood stream without being targeted for removal. This allows the nanoshells to travel in
the bloodstream longer increasing the chance they come across cancer cells. The biology
of cancer cells also helps nanoshells find them.

Cancer cells grow faster than normal cells and because of it they are leaky and allow
particles the size of the gold nanoshells to pass through them. The leakiness of the cancer
cells require more blood to pass through them, so there is more chance that the nanoshells
go their sooner. Because cancer cells grow faster than normal cells, cancer cells have
more epidermal growth factor receptors (EGFR) than healthy cells. EGFR are on the
surface of the cell and combine to things in the body that cause the cancer cell to grow.
Nanoshells are coated with anitepidermal growth factor receptor, or anti-EGFR for short,
which combine with the EGFR and bind the nanoshell to the cancer cell. Nanoshells will
continue binding with the cancer cell until about 20 nanoshells are connected to each
cancer cell. At this point, the nanoshells are ready to start imaging and treating the cancer
cells they are bound to.

Gold Nanoshells Cancer Imaging:

Early detection of cancer is often important for effective treatment. The best way to
detect cancer early is to use effective imaging techniques to search for any potential
dangers that might be developing in a patient. Unfortunately, current imaging methods
are not clear enough to show the early signs of cancer and dangerous cell mutations that
are required for doctors to identify problems.

One method that allows easier detection of cancer is to attach "markers" that target cancer
cells. The markers outline or cover the cancer cell, showing both its size and shape.
Markers are more reflective than the cancer cells, making the cells more noticeable than
they otherwise are. Ideal markers are small, durable, biocompatible particles that only
bind to the area of interest. Gold nanoshells make excellent optical markers for cancer
because they are small, inert (gold doesn't react with the body's biology), and can be
fabricated to bind to cancer cells. It may seem strange to think that a nanoshell, which is
too small to be seen with the human eye, can be used as an optical marker to show
something much larger than them, yet their size, shape, and material give them unique
optical properties. Gold nanoshells are especially useful as biological markers because
they can be tuned to scatter near-infrared light, which fits in the "water-window" of the
body.

During their creation, gold nanoshells are made to be about 100x smaller than most
cancer cells and coated with cell receptors that connect to cancer cells. When the
nanoshells attach to the cancer cell, they bind to the outside of the cancer cell. Enough of
the nanoshells will bind to a cancer cell that nanoshells will cover the cancer cell. Since
the nanoshells are small and cover the cancer cell, imaging the nanoshells is just like
imaging the cancer cell. Nanoshells are small enough to achieve a high quality image of
the area they attach to. Also, nanoshells use their ability to redirect light to act as a
reflector, allowing for a number of quick and efficient imaging techniques.

Due to their small size and dimensions, nanoshells have the ability to redirect light in
many different directions, also known as scattering light. Nanoshells are tuned to scatter
specific wavelengths of light when they are created. The scattered wavelength is
determined by the size of the nanoshell and the intensity is enhanced due to the gold
coating. This property makes optical imaging of cancer cells effective.

Imaging is useful because it allows the doctor to correctly determine which cells are
healthy and which cells are cancerous. With the cancerous cells now identified, treatment
can begin. The process that allows cancer cells to be imaged also allows cancer treatment.
Fortunately, many of the properties that make nanoshells excellent markers also make
them good agents for treating cancer.

Gold Nanoshells Extensions:

Currently the use of gold nanoshells is restricted to lab settings. While the procedure is
promising, it is not old enough or well studied enough to provide for clinical testing.
However, proposals have been made to the FDA requesting approval for clinical trials of
using gold nanoshells to image and ablate cancer.

Gold nanoshells are not the only nanoscale-based cancer detection and treatments being
investigated. Scientists across the world are using different kinds of nanoparticles to
provide new imaging and cancer therapies. One of these alternative therapies uses iron
nanoparticles to detect prostate cancer through combined use with MRI technology.
Other studies are investigating the use of gold nanoparticles (not nanoshells) to deliver
anti-cancer drugs to specific cell sites. While the iron based prostate cancer detection
method offers a more specific detection regimen, it does not provide a means to fight
existing cancer, and immunotargeted nanoparticles run the risk of presenting anti-cancer
drugs to healthy cells (something that is not desirable under any circumstance). No
treatment is without cause for some concern, but certainly each new discovery offers
promising contributions to the fight against cancer.

This research also lends itself to other applications outside of the realm of cancer. These
applications include but are not limited to fusing tissue together without stitches,
providing new imaging techniques for cells and DNA, as well as acting as biomarkers for
specific biological agents.

Conclusion:

As mentioned in previous sections, as of 2007, gold nanoshells have not been tested in a
clinical environment. However, they offer increasingly promising results in lab studies
with no significant side effects. Gold nanoshells are fast becoming the forerunner of other
nanomedicine technologies, and their success could provide medical professionals with
some special tools to fight disease.

Abbreviations:

EGFR: Epidermal growth factor receptors

PEG: poly ethylene glycol

FDA: food drug association

DNA: deoxy ribose nucleic acid

EM waves: electro magnetic waves

References:

1. Franks, G.V. and Lange, F.F., J. Am. Ceram. Soc., Vol.79, p.3161 (1996)

2. Evans, A.G. and Davidge, R.W., Phil. Mag., Vol.20, p.164 (1969) ; J Mat. Sci., Vol.5,
p.314 (1970)

3. Lange, F.F. and Metcalf, M., J. Am. Ceram. Soc., Vol.66, p.398 (1983)

4. Nanotechnology web page.

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SANTOSH BHARADWAJ REDDY
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