24-01-2010, 04:59 PM
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NANOTECHNOLOGY CRITICAL ENDEAVOR IN CANCER
1.0 ABSTRACT
The advent of nanotechnology in cancer
research couldnâ„¢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 todayâ„¢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 substratesâ€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.
