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BNCE PUSAD

NANOTECHNOLOGY FOR CANCER

THERAPY

Ritesh Bhusari
10/4/2005

btritesh@yahoo.com

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1. INTRODUCTION:-

Nanotechnology is the creation of useful materials, devices, and system

used to manipulate matter at an incredibly small scale -- between 1 and 100 nanometers.

A nanometer is one billionth of a meter - 1/80,000 the width of a human

hair, or about ten times the diameter of a hydrogen atom. Such nanoscale objects can be
useful by themselves, or as part of larger devices containing multiple nanoscale objects.

Nanotechnology has the potential to enable the translation of molecular-

based science into clinical advances, thereby facilitating major progress in the early
detection, diagnosis and treatment of cancer.

Nanoscale devices are the same size as many important biological

objects, and therefore can be used to “see” biological activity that the naked eye cannot.
They can perform tasks inside the body that would otherwise not be possible. Nanoscale
devices are smaller than human cells, which are 10,000 to 20,000 nanometers in
diameter, and cellular components such as mitochondria that are inside cells.

Imagine curing cancer by drinking a medicine stirred into your favourite

juice. A supercomputer no bigger than a human cell. A space craft no larger or more
expensive than family car. These are the few promises of nanotechnology.

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2. NEED OF NANOTECHNOLOGY IN CANCER TREATMENT :-

There are several reasons that nanotechnology could help transform

cancer research and clinical approaches to cancer care:

Most biological processes, including those processes leading to cancer,

occur at the nanoscale. For cancer researchers, the ability of nanoscale devices to easily
access the interior of a living cell affords the opportunity for unprecedented gains on
both clinical and basic research frontiers.

The ability to simultaneously interact with multiple critical proteins and

nucleic acids at the molecular level will provide a better understanding of the complex
regulatory and signaling patterns that govern the behavior of cells in their normal state
as well as the transformation into malignant cells.

Nanotechnology provides a platform for integrating research in

proteomics -- the study of the structure and function of proteins, including the way they
work and interact with each other inside cells -- with other scientific investigations into
the molecular nature of cancer.

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3. NANOTECHNOLOGY PLATFORM FOR CANCER RESEARCH :-

Using Broad Agency Announcements (BAAs), NCI will identify to the R&D
community critical technology platform needs for cancer, such as in vivo nanotechnology
imaging systems and nanotechnology-enabled systems for rapidly assessing therapeutic
efficacy and addressing cancer biology processes. The program will fund 3-year technology
projects through a contract mechanism that is overseen by project specialists. The project will
target cancer centers, small businesses, and Federal laboratories that prepare and submit
concepts and project objectives.

Upon review of initial submissions, full solicitations will be sought from those
of highest value. Technology programs will create platforms that are aimed at deployment for
clinical application in cancer research. Applicants will be required to team with the
Comprehensive Cancer Centers or SPOREs with a plan for dissemination of the technology.

4. MODES OF ITS IMPLEMENTATION :-

4.1 Molecular Imaging And Early Detection :-

Nanotechnology can have an early, paradigm-changing impact on how clinicians

will detect cancer in its earliest stages. Exquisitely sensitive devices constructed of nanoscale
components-such as nanocantilevers, nanowires, and nanochannels-offer the potential for
detecting even the rarest molecular signals associated with malignancy. Collecting those signals
for analysis could fall to nanoscale harvesters, already under development, that selectively
isolate cancer-related molecules such as proteins and peptides present in minute amounts from
the bloodstream or lymphatic system. Investigators have already demonstrated the feasibility of
this approach using the serum protein albumin (a naturally nanoparticle), which happens to
collect proteins that can signal the presence of malignant ovarian tissue.

Another area with near-term potential is detecting mutations and genome

instability in situ. Already, investigators have developed novel nanoscale in vitro techniques
that can analyze genomic variations across different tumor types and distinguish normal from
malignant cells. Nanopores are finding use as real-time DNA sequencers, and nanotubes are
showing promise in detecting mutations using a scanning electron microscope. Further work
could result in a nanoscale system capable of differentiating among different types of tumors
accurately and quickly, information that would be invaluable to clinicians and researchers alike.
Along similar lines, other investigators have developed nanoscale technologies capable of
determining protein expression patterns directly from tissue using mass spectroscopy. This
technique has already shown that it can identify different types of cancer and provide data that
correlate with clinical prognosis.

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In addition, nanoscale devices can enable new approaches for real-time

monitoring of exposures to environmental and lifestyle cancer risk factors. Such information
would be important not only for identifying individuals who may be at risk for developing
cancer, but also for opening the door to complex studies of gene-environment interactions as
they relate to the development of or resistance to cancer.

4.2 In vivo imaging :-

One of the most pressing needs in clinical oncology is for imaging agents that
can identify tumors that are far smaller than is possible with today's technology, at a scale of
100,000 cells rather than 1,000,000,000 cells. Achieving this level of sensitivity requires better
targeting of imaging agents and generation of a bigger imaging signal, both of which nanoscale
devices are capable of accomplishing. When attached to a dendrimer, for example, the MRI
contrast agent gadolinium generates a 50-fold stronger signal than in its usual form, and given
that nanoscale particles can host multiple gadolinium ions, affords an opportunity to create a
powerful contrast agent. When linked to one of the increasing number of targeting agents, such
a construct would have the potential of meeting the 100,000 cell detection level.

First-generation nanoscale imaging contrast agents are already pointing the way
to new methods for spotting tumors and metastatic lesions much earlier in their development,
before they are even visible to the eye. In the future, implantable nanoscale biomolecular
sensors may enable clinicians to more carefully monitor the disease-free status of patients who
have undergone treatment or individuals susceptible to cancer because of various risk factors.

Imaging agents should also be targeted to changes that occur in the environment
surrounding a tumor, such as angiogenesis, that are now beyond our capability to detect in the
human body. Already, various nanoparticles are being targeted to integrins expressed by
growing capillaries. Given that angiogenesis occurs in distinct stages and that antiangiogenic
therapies will need to be specific for a given angiogenic state, angiogenesis imaging agents that
can distinguish among these stages will be invaluable to obtain optimal benefit from
therapeutics that target angiogenesis.

4.3 Reporters Of Efficacy :-

Today, clinicians and patients must often wait months for signs that a given
therapy is working. In many instances, this delay means that should the initial therapy fail,
subsequent treatments may have a reduced chance of success. This lag also adversely impacts
how new therapies undergo clinical testing, since it leaves regulatory agencies reluctant to
allow new cancer therapies to be tested on anyone but those patients who have exhausted all
other therapeutic possibilities. Unfortunately, this set of patients is far less likely to respond to
any therapy, particularly to those molecularly targeted therapies that aim to stop cancer early in
its progression, an approach that virtually all of our knowledge says is the best approach for
treating cancer.

Nanotechnology offers the potential to develop highly sensitive imaging agents

and diagnostics that can determine whether a therapeutic agent is reaching its intended target

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and whether that agent is killing malignant or support cells, such as growing blood vessels.
Targeted nanoscale devices may also enable surgeons to more readily detect the margins of a
tumor prior to resection or to detect micro metastases in lymph nodes or tissues distant from the
primary tumor, information that would inform therapeutic decisions and have a positive impact
on patient quality-of-life issues.

The greatest potential for immediate results in this area would focus on detecting
apoptosis following cancer therapy. Such systems could be constructed using nanoparticles
containing an imaging contrast agent and a targeting molecule that recognizes a biochemical
signal only seen when cells undergo apoptosis. Using the molecule annexin V as the targeting
ligand attached to nanoscale iron oxide particles.

5 DEVICES IT IMPLEMENT :-

5.1 NANOWIRE SENSOR :-

Reference: Jim Heath, California Institute of Technology

In this diagram, nano sized sensing wires are laid down across a microfluidic
channel. These nanowires by nature have incredible properties of selectivity and specificity. As
particles flow through the microfluidic channel, the nanowire sensors pick up the molecular
signatures of these particles and can immediately relay this information through a connection of
electrodes to the outside world.

These nanodevices are man-made constructs made with carbon, silicon and
other materials that have the capability to monitor the complexity of biological phenomenon
and relay the information, as it is monitored, to the medical care provider.

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5.2 NANOSCALE CANTILEVER :–

Reference: Jennifer West, Rice University

Nanoscale cantilevers – microscopic, flexible beams resembling a row of diving

boards – are built using semiconductor lithographic techniques. These can be coated with
molecules capable of binding specific substrates—DNA complementary to a specific gene
sequence, for example. Such micron-sized devices, comprising many nanometer-sized
cantilevers, can detect single molecules of DNA or protein.

As a cancer cell secretes its molecular products, the antibodies coated on the
cantilever fingers selectively bind to these secreted proteins. These antibodies have been
designed to pick up one or more different, specific molecular expressions from a cancer cell.
The physical properties of the cantilevers change as a result of the binding event. Researchers
can read this change in real time and provide not only information about the presence and the
absence but also the concentration of different molecular expressions. Nanoscale cantilevers,
constructed as part of a larger diagnostic device, can provide rapid and sensitive detection of
cancer-related molecule.

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5.3 NANOSHELL :-

Reference: Jennifer West, Rice University

Nanoshells have a core of silica and a metallic outer layer. These nanoshells can
be injected safely, as demonstrated in animal models.

Because of their size, nanoshells will preferentially concentrate in cancer lesion

sites. This physical selectivity occurs through a phenomenon called enhanced permeation
retention (EPR).Scientists can further decorate the nanoshells to carry molecular conjugates to
the antigens that are expressed on the cancer cells themselves or in the tumor
microenvironment. This second degree of specificity preferentially links the nanoshells to the
tumor and not to neighboring healthy cells.

As shown in this example, scientists can then externally supply energy to these
cells. The specific properties associated with nanoshells allow for the absorption of this
directed energy, creating an intense heat that selectively kills the tumor cells. The external
energy can be mechanical, radio frequency, optical – the therapeutic action is the same.

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6. SUCCESS OF NANOTECHNOLOGY IMPLEMENTATION :-

The field of nanotechnology has already yielded specific products and

proofs of principle demonstrated to be of value in clinical applications:

Liposomes, which are first generation nanoscale devices, are being used
as drug delivery vehicles in several products. For example, liposomal amphotericin B is
used to treat fungal infections often associated with aggressive anticancer treatment and
liposomal doxorubicin is used to treat some forms of cancer.

Another recent example is work done by researchers at Massachusetts

General Hospital, led by Ralph Weissleder, M.D., Ph.D., which has shown that
nanoparticulate iron oxide particles can be used with magnetic resonance imaging
(MRI) to accurately detect metastatic lesions in lymph nodes without surgery.

In May 2004, two companies (American Pharmaceutical Partners and

American BioScience) announced that the FDA accepted the filing of a New Drug
Application (NDA) for a nanoparticulate formulation of the anticancer compound taxol
to treat advanced stage breast cancer. Earlier-stage research has shown that
nanoparticulate sensors can detect the cell death that occurs when a cancer cell
succumbs to the effects of an anticancer drug. Such sensors would be of great value to
clinicians, who would no longer have to wait months to determine if a cancer therapy is
working before switching a patient to a course of therapy. In addition, such a sensor
could greatly accelerate clinical trials of new anticancer agents, again by providing very
early signals of efficacy.

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7. PROMIISE OF NANOTECHNOLGY :-

Nanotechnology offers a wealth of tools that are providing cancer

researchers with new and innovative ways to diagnose and treat cancer. Already,
nanotechnology has been used to create new and improved ways to find small tumors
through imaging. Nanoscale drug delivery devices are being developed to deliver
anticancer therapeutics specifically to tumors. Work is currently being done to move
these new research tools into clinical practiceIn the near future, nanoscale devices could
offer the potential to detect cancer at its earliest stage and simultaneously deliver
anticancer agents to the discovered tumor. Indeed, nanoscale devices could be the
crucial enabling technology that will turn the promise of personalized cancer therapy --
where a patient receives a drug based on the exact genetic and molecular characteristics
of his or her particular type of cancer -- into reality.

Nanotechnology provides opportunities to prevent cancer progression.

For example, nanoscale systems, because of their small dimensions, could be applied to
stop progression of ductal types of breast cancers.

Nanoscale cantilevers and nanowire sensors can detect biomarkers of

cancer from a single cell , which heretofore was unimaginable. Nanoparticles can aid in
imaging malignant lesions, so surgeons know where the cancer is, and how to remove
it. Nanoshells can kill tumor cells selectively, so patients don’t suffer terrible side
effects from healthy cells being destroyed. Dendrimers can sequester drugs to reduce
systemic side effects, deliver multiple drugs to maximize therapeutic impact, and
rapidly discern effectiveness of a drug. Biosensors can monitor genetic changes and
hyperplasia to prevent cancer progression.

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8. CONCLUSION :-

The application discussed here is speculative. Nanotechnology ,with all it’s challenges
and opportunities, is an unavoidable part of our future.The possibilities with nanotechnology are
immense and numerous. The researchers are filled with optimism, and products based on this
technology are beginning to make their mark. The extent to which nanotechnology will impact our
lives only depend on the limits of human ingenuinity.

Expanding computer and information technology capabilities for manipulating vast

amounts of clinical and biological data . Advances in nanotechnology itself that make it feasible to
develop devices for imaging and delivering drugs. As nanotechnology progress we may except
application to become feasible at a slowly increasingly rate.

Now, Nanotechnology, specifically biomedical nanotechnology, may be advancing too

fast, ensuring that the technology is safe and effective. The success of efforts in the field is contingent
upon scientific excellence in research and development that is both ethical and safe for the body and
the environment.

“It can be rightly to be said that nanotechnology is slowly but steadily

ushering in the next industrial revolution.”

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9. REFERENCES :-

1. “NANOTECHNOLOGY shaping the future” (page no.40) ELECTRONICS FOR YOU-AUG 04

2. http://www.nano.cancer.gov

3. http://www.videocast.nih.gov/PastEvents.asp.

4. http://www.google.com/applications+nanotechnology

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