NANOTECHNOLOGY

CRITICAL ENDEAVOR IN CANCER

1.0 ABSTRACT

The advent of nanotechnology in cancer research couldn’t have come at a

more opportune time. The vast knowledge of cancer genomics and proteomics
emerging as a result of the Human Genome Project is providing critically important
details of how cancer develops, which, in turn, creates new opportunities to attack
the molecular underpinnings of cancer. However, scientists lack the technological
innovations to turn promising molecular discoveries into benefits for cancer
patients. It is here that nanotechnology can play a pivotal role, providing the
technological power and tools that will enable those developing new diagnostics,
therapeutics, and preventives to keep pace with today’s explosion in knowledge.

Nanotechnology provides the sized materials that can be synthesized and

function in the same general size range and Biologic structures. Attempts are
made to develop forms of anticancer therapeutics based on nanomaterials.
Dendritic polymer nanodevices serves as a means for the detection of cancer cells,
the identification of cancer signatures, and the targeted delivery of anti-cancer
therapeutics (cis-platin, methotrexate, and taxol) and contrast agents to tumor
cells. Initial studies documented the synthesis and function of a targeting module,
several drug delivery components, and two imaging/contrast agents. Analytical
techniques have been developed and used to confirm the structure of the device.
Progress has been made on the specifically triggered release of the therapeutic
agent within a tumor using high-energy lasers. The work to date has demonstrated
the feasibility of the nano-device concept in actual cancer cells in vitro.
 2.0 INTRODUCTION

Nanotechnology offers the unprecedented and paradigm-changing

opportunity to study and interact with normal and cancer cells in real time, at
the molecular and cellular scales, and during the earliest stages of the cancer
process. Through the concerted development of nanoscale devices or devices
with nanoscale materials and components, the NCI Alliance for
Nanotechnology in Cancer will facilitate their integration within the existing
cancer research infrastructure. The Alliance will bring enabling technologies for:

• Imaging agents and diagnostics that will allow clinicians to detect cancer
earliest stages
• Systems that will provide real-time assessments of therapeutic and surgical
efficacy for accelerating clinical translation
• Multifunctional, targeted devices capable of bypassing biological barriers to
deliver multiple therapeutic agents directly to cancer cells and those tissues in
the microenvironment that play a critical role in the growth and metastasis of
cancer .
• Agents that can monitor predictive molecular changes and prevent
precancerous cells from becoming malignant
• Novel methods to manage the symptoms of cancer that adversely impact
quality of life
• Research tools that will enable rapid identification of new targets for clinical
development and predict drug resistance.

3.0 NANOTECHNOLOGY IN CANCER

Nanoscale devices are somewhere from one hundred to ten thousand

times smaller than human cells. They are similar in size to large biological
molecules ("biomolecules") such as enzymes and receptors. As an example,
hemoglobin, the molecule that carries oxygen in red blood cells, is
approximately 5 nanometers in diameter. Nanoscale devices smaller than 50
nanometers can easily enter most cells, while those smaller than 20
nanometers can move out of blood vessels as they circulate through the body.

Because of their small size, nanoscale devices can readily interact with
biomolecules on both the surface of cells and inside of cells. By gaining access
to so many areas of the body, they have the potential to detect disease and
deliver treatment in ways unimagined before now. And since biological
processes, including events that lead to cancer, occur at the nanoscale at and
inside cells, nanotechnology offers a wealth of tools that are providing cancer
researchers with new and innovative ways to diagnose and treat cancer.
4.0 NANOTECHNOLOGY AND CANCER THERAPY

Nanoscale devices have the potential to radically change cancer

therapy for the better and to dramatically increase the number of highly
effective therapeutic agents. Nanoscale constructs can serve as customizable,
targeted drug delivery vehicles capable of ferrying large doses of
chemotherapeutic agents or therapeutic genes into malignant cells while
sparing healthy cells,greatly reducing or eliminating the often unpalatable side
effects that accompany many current cancer therapies.

On an equally unconventional front, efforts are focused on

constructing robust “smart” nanostructures that Will eventually be capable of
detecting malignant cells in vivo, pinpointing their location in the body, killing
the cells, and reporting back that their payload has done its job. The operative
principles driving these current efforts are modularity and multifunctionality, i.e.,
creating functional building blocks that can be snapped together and modified
to meet the particular demands of a given clinical situation.

5.0 NANOWIRES

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.

They can detect the presence of altered genes associated with

cancer and may help researchers pinpoint the exact location of those changes
6.0 CANTILEVERS

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. Researcherscan 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 molecules.

7.0 NANOSHELLS

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.The result is greater
efficacy of the therapeutic treatment and a significantly reduced set of side
effects.

8.0 NANOPARTICLES

Nanoscale devices have the potential to radically change cancer

therapy for the better and to dramatically increase the number of highly
effective therapeutic agents.In this example, nanoparticles are targeted to
cancer cells for use in the molecular imaging of a malignant lesion. Large
numbers of nanoparticles are safely injected into the body and preferentially
bind to the cancer cell, defining the anatomical contour of the lesion and
making it visible.

These nanoparticles give us the ability to see cells and molecules that
we otherwise cannot detect through conventional imaging. The ability to pick up
what happens in the cell — to monitor therapeutic intervention and to see when
a cancer cell is mortally wounded or is actually activated — is critical to the
successful diagnosis and treatment of the disease.

Nanoparticulate technology can prove to be very useful in cancer

therapy allowing for effective and targeted drug delivery by overcoming the
many biological, biophysical and biomedical barriers that the body stages
against a standard intervention such as the administration of drugs or contrast
agents.
9.0 CHALLENGES

The six major challenge areas of emphasis include:

9.1 Prevention and Control of Cancer:
• Developing nanoscale devices that can deliver cancer prevention agents
• Designing multicomponent anticancer vaccines using nanoscale
delivery vehicles
9.2 Early Detection and Proteomics:
• Creating implantable, biofouling-indifferent molecular sensors that can
detect cancer-associated biomarkers that can be collected for ex vivo
analysis or analyzed in situ, with the results being transmitted via
wireless technology to the physician
• Developing “smart” collection platforms for simultaneous mass
spectroscopic analysis of multiple cancer-associated markers.
9.3 Imaging Diagnostics:
• Designing “smart” injectable, targeted contrast agents that improve the
resolution of cancer to the single cell level
• Engineering nanoscale devices capable of addressing the biological and
evolutionary diversity of the multiple cancer cells that make up a tumor
within an individual.
9.4 Multifunctional Therapeutics:
• Developing nanoscale devices that integrate diagnostic and therapeutic
functions
• Creating “smart” therapeutic devices that can control the spatial and
temporal release of therapeutic agents while monitoring the
effectiveness of these agents
9.5 Quality of Life Enhancement in Cancer:
• Designing nanoscale devices that can optimally deliver medications for
treating conditions that may arise over time with chronic anticancer
therapy, including pain, nausea, loss of appetite, depression, and
difficulty breathing.
9.6 Interdisciplinary Training:
• Coordinating efforts to provide cross-training in molecular and systems
biology to nanotechnology engineers and in nanotechnology to cancer
researchers.
• Creating new interdisciplinary coursework/degree programs to train a
new generation of researchers skilled in both cancer biology and
nanotechnology.
10.0 CONCLUSION

Work is currently being done to find ways to safely move

these new research tools into clinical practice. Today, cancer-related
nanotechnology is proceeding on two main fronts: laboratory-based
diagnostics and in vivo diagnostics and therapeutics.

Nanodevices can provide rapid and sensitive detection of

cancer-related molecules byenabling scientists to detect molecular
changes even when they occur only in a small percentage of cells.
Nanotechnology is providing a critical bridge between the physical
sciences and engineering, on the one hand, and modern molecular
biology on the other. Materials scientists, for example, are learning the
principles of the nanoscale world by studying the behavior of
biomolecules and biomolecular assemblies. In return, engineers are
creating a host of nanoscale tools that are required to develop the
systems biology models of malignancy needed to better diagnose, treat,
and ultimately prevent cancer. In particular, biomedical nanotechnology
is benefiting from the combined efforts of scientists from a wide range of
disciplines, in both the physical and biological sciences, who together
are producing many different types and sizes of nanoscale devices, each
with its own useful characteristics.