Going Small for Big Advances*Using Nanotechnology to Advance ...

cancer NANOTECHNOLOGY
Going Small for Big Advances
Using Nanotechnology to Advance
Cancer Diagnosis, Prevention
and Treatment
U.S. DEPARTMENT OF
HEALTH AND HUMAN SERVICES
National Institutes of Health
National Cancer Institute
January 2004

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NaNotechNology aNd caNcer
To help meet the goal of eliminating death and suffering
from cancer by 2015, the National Cancer Institute is engaged
in efforts to harness the power of nanotechnology to
radically change the way we diagnose, image, and treat
cancer. Already, NCI programs have supported research
Nanotechnology will change the very
foundations of cancer diagnosis, treatment,
and prevention.
on novel nanodevices capable of one or more clinically
important functions, including detecting cancer at its
earliest stages, pinpointing its location within the body,
delivering anticancer drugs specifically to malignant cells,
and determining if these drugs are killing malignant cells.
As these nanodevices are evaluated in clinical trials, researchers
envision that nanotechnology will serve as multifunctional
tools that will not only be used with any number of diagnostic
and therapeutic agents, but will change the very foundations
of cancer diagnosis, treatment, and prevention.
cancer Nanotechnology
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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.
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To harness the potential of nanotechnology in cancer,
NCI is seeking broad scientific input to provide direction
to research and engineering applications. In doing so,
NCI will develop a Cancer Nanotechnology Plan. Drafted
with input from experts in both cancer research and
nanotechnology, the Plan (see pages 4 and 5) will guide
To harness the potential of nanotechnology
in cancer, NCI is seeking broad scientific input
to provide direction to research and
engineering applications.
NCI in supporting the interdisciplinary efforts needed to
turn the promise of nanotechnology and the postgenomics
revolution in knowledge into dramatic gains in our ability
to diagnose, treat, and prevent cancer. Though this quest
is near its beginning, the following pages highlight some of
the significant advances that have already occurred from
bridging the interface between modern molecular biology
and nanotechnology.
cancer Nanotechnology
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developiNg a caNcer
NaNotechNology plaN
NCI’s Cancer Nanotechnology Plan will provide critical
support for the field though extramural projects, intramural
programs, and a new Nanotechnology Standardization
Laboratory. This latter facility will develop important
standards for nanotechnological constructs and devices that
will enable researchers to develop cross-functional platforms
that will serve multiple purposes. The laboratory will be a
centralized characterization laboratory capable of generating
technical data that will assist researchers in choosing which
of the many promising nanoscale devices they might want
to use for a particular clinical or research application. In
addition, this new laboratory will facilitate the development
of data to support regulatory sciences for the translation
of nanotechnology into clinical applications.
The six major challenge areas of emphasis include:
Prevention and Control of Cancer
• Developing nanoscale devices that can deliver cancer
prevention agents
• Designing multicomponent anticancer vaccines using
nanoscale delivery vehicles
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
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• Developing “smart” collection platforms for
simultaneous mass spectroscopic analysis of multiple
cancer-associated markers
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
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
Quality of Life Enhancement in Cancer Care
• 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
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
cancer Nanotechnology
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What is NaNotechNology?
Nanotechnology refers to the interactions of cellular and
molecular components and engineered materials—typically
clusters of atoms, molecules, and molecular fragments—at
the most elemental level of biology. Such nanoscale objects—
typically, though not exclusively, with dimensions smaller
than 100 nanometers—can be useful by themselves or as
part of larger devices containing multiple nanoscale objects.
At the nanoscale, the physical, chemical, and biological
properties of materials differ fundamentally and often
Noninvasive access to the interior of a living cell
affords the opportunity for unprecedented gains
on both clinical and basic research frontiers.
unexpectedly from those of the corresponding bulk
material because the quantum mechanical properties of
atomic interactions are influenced by material variations
on the nanometer scale. In fact, by creating nanometer-
scale structures, it is possible to control fundamental
characteristics of a material, including its melting point,
magnetic properties, and even color, without changing
the material’s chemical composition.
Nanoscale devices and nanoscale components of larger
devices are of the same size as biological entities. They are
smaller than human cells (10,000 to 20,000 nanometers
in diameter) and organelles and similar in size to large
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biological macromolecules such as enzymes and receptors—
hemoglobin, for example, is approximately 5 nm in diameter,
while the lipid bilayer surrounding cells is on the order of
6 nm thick. Nanoscale devices smaller than 50 nanometers
can easily enter most cells, while those smaller than 20
nanometers can transit out of blood vessels. As a result,
nanoscale devices can readily interact with biomolecules
on both the cell surface and within the cell, often in ways
that do not alter the behavior and biochemical properties
of those molecules. From a scientific viewpoint, the actual
construction and characterization of nanoscale devices may
contribute to understanding carcinogenesis.
Noninvasive access to 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 scale should provide better understanding
of the complex regulatory and signaling networks that
govern the behavior of cells in their normal state and as
they undergo malignant transformation. Nanotechnology
cancer Nanotechnology
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provides a platform for integrating efforts in proteomics
with other scientific investigations into the molecular
nature of cancer by giving researchers the opportunity
to simultaneously measure gene and protein expression,
recognize specific protein structures and structural domains,
and follow protein transport among different cellular
compartments. Similarly, nanoscale devices are already
proving that they can deliver therapeutic agents that
can act where they are likely to be most effective, that
is, within the cell or even within specific organelles. Yet
despite their small size, nanoscale devices can also hold
tens of thousands of small molecules, such as a contrast
agent or a multicomponent diagnostic system capable of
assaying a cell’s metabolic state, creating the opportunity
for unmatched sensitivity in detecting cancer in its earliest
stages. For example, current approaches may link a monoclonal
antibody to a single molecule of an MRI contrast agent,
requiring that many hundreds or thousands of this construct
reach and bind to a targeted cancer cell in order to create a
strong enough signal to be detected via MRI. Now imagine
the same cancer-homing monoclonal antibody attached to
a nanoparticle that contains tens of thousands of the same
contrast agent—if even one such construct reaches and
binds to a cancer cell, it would be detectable.
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