Nanotechnology
in Medicine (Nanomedicine)
Nanomedicine
is the medical use of molecular-sized particles to deliver drugs,
heat, light or other substances to specific cells in the human body.
Engineering particles to be used in this way allows detection and/or
treatment of diseases or injuries within the targeted cells, thereby
minimizing the damage to healthy cells in the body.
Nanotechnology
Characterization Lab
Eliminating suffering and
death from cancer requires an unprecedented collaborative effort that
leverages resources from government, industry, and academia. Working in
concert with the National Institute of Standards and Technology (NIST) and
the U.S. Food and Drug Administration (FDA), the National Cancer Institute
(NCI) established the Nanotechnology Characterization Laboratory to
perform preclinical efficacy and toxicity testing of nanoparticles.
The NCL serves as a national
resource and knowledge base for all cancer researchers to facilitate the
regulatory review of nanotechnologies intended for cancer therapies and
diagnostics. By providing the critical infrastructure and characterization
services to nanomaterial providers, the NCL accelerates the transition of
basic nanoscale particles and devices into clinical applications, thereby
reducing suffering and death from cancer.
As part of its assay
cascade, the NCL characterizes nanoparticles' physical
attributes, their in vitro
biological properties, and their in
vivo compatibility using animal
models. The time required to characterize nanomaterials from receipt
through the in vivo
phase is approximately one year.
Exploring
Nanotechnology in Cancer
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:
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Imaging agents and diagnostics that will allow clinicians to detect cancer in its earliest stages
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Systems that will provide real-time assessments of therapeutic and surgical efficacy for accelerating clinical translation
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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
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Agents that can monitor predictive molecular changes and prevent precancerous cells from becoming malignant
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Novel methods to manage the symptoms of cancer that adversely impact quality of life
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Research tools that will enable rapid identification of new targets for clinical development and predict drug resistance
Effects of nanotechnology on the environment
11
Mar 2004
The use of nanotechnology to create
new types of miniature sensors, pollutant filters and fuel cell catalysts
could benefit the environment, according to evidence, published today (11
March 2004), that is being considered by the Royal Society and Royal
Academy of Engineering working group on nanotechnology. However, the
testimony from industry and academic experts and regulators suggests there
is still uncertainty about the impact of releasing nanoparticles into the
environment.
Commenting on the evidence, Professor Ann Dowling, chair of the working
group on nanotechnology, said: "The working group has been told that
nanotechnology is being used to develop applications that may benefit the
environment through, for instance, helping to detect and filter out
pollutants. It has also been pointed out to us that we still have a lot to
learn about how nanoparticles behave when they are released into the
environment. There are already many natural and man-made sources of
nanoparticles, such as diesel and welding fumes."
She added: "The evidence that we have received so far, including the
testimony at the workshop, has suggested that relatively little is known
about the likely overall positive and negative environmental impacts of
nanotechnology, and we are now consulting more widely to establish how
true this is. The working group is casting its net widely for evidence
during the course of its study and continuing to listen to different
viewpoints as part of its ongoing work before publication of the report in
summer 2004.
A paint industry representative at the workshop indicated that
nanoparticles could be incorporated in energy-saving coatings that would
help to reduce heat loss by reflecting infra-red radiation, or to produce
’smart paints’ that change colour when exposed to changes in
temperature or light. However, these products were likely to be more
expensive than those currently available, and it was possible that they
could become a source of nanoparticles in the environment as the paints
eroded.
According to a representative from the telecoms industry, nanotechnology
could make the use of materials in manufacturing more efficient and could
advance the miniaturisation of sensors with a wide range of applications
from monitoring agricultural chemicals to easing the flow of traffic.
Miniature sensors developed through nanotechnology could also be used to
detect specific pollutants accidentally or deliberately released into the
environment. The removal of pollutants may be achieved through filters
incorporating nanoparticles, the first of which may be available within a
couple of years. Nanotechnology might also be used in catalysts that
promote key chemical reactions within fuel cells that might be used with
sources of renewable energy.
The working group also discussed with the workshop participants whether
regulations governing the release of nanoparticles into the environment
were felt to be adequate. It was noted that nanoparticles had some special
properties because of their small size, and that these might not be fully
taken into account in current regulations.
Notes for Editors
1. The Office of Science and Technology commissioned the Royal Society and
the Royal Academy of Engineering in July 2003 to carry out a study to:
- define what is meant by nanoscience and nanotechnology;
- summarise the current scientific knowledge on nanotechnology;
- identify applications of nanotechnology, both currently and potentially,
with indications of when they might be developed;
- consider environmental, health and safety, ethical and social
implications of the technology, both now and in the future;
- suggest areas where additional regulation should be considered.
The report of the study will be published in summer 2004.
2. The objectives
of the Royal Society.
3. Founded in 1976, the Royal Academy of Engineering promotes the
engineering and technological welfare of the country. Its fellowship -
comprising the UK’s most eminent engineers - provides the leadership and
expertise for its activities, which focus on the relationships between
engineering, technology, and the quality of life. As a national academy,
it provides independent and impartial advice to Government; works to
secure the next generation of engineers; and provides a voice for
Britain’s engineering community.
NANOTECHNOLOGY
Exploring the World of Nano Medical Devices
Offering
the possibilities of smaller, lighter, and faster materials and devices,
nanotechnology is working its way into the world of medtech.
Max Sherman
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Gold
nanorods, which fluoresce red, were photographed inside
the blood vessels of a live mouse by researchers at Purdue’s
Weldon School of Biomedical Engineering and department of chemistry.
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The word nanotechnology was conceived by
Norio Taniguchi in 1974 to signify machining with tolerances of less than
a micron.1 Since then, nanotechnology has taken on a new
meaning. It is now defined as the world of controlling matter at the
nanometer (one billionth of a meter) scale.
Nanotechnology is expected to become the
transformational technology of this century. Materials fabricated at a
nanoscale, i.e., nanomaterials, have different and often amazing
properties that can be used to restructure manufacturing, energy
production, and a host of other fields.2 Such materials
typically have nanostructure-dependent properties (e.g., chemical,
mechanical, electrical, biological, optical or magnetic), which make them
desirable for medical applications.
Nanotechnology can offer solutions to many
current problems by means of smaller, lighter, faster, and
better-performing materials, components, and systems. Nanomaterials are
being used in computers, cosmetics, stain-resistant fabrics, sports
equipment, paints, and medical diagnostic tests. It is essential to
understand the definitions that pertain to this new field, the
fundamentals of nanomaterials, and current and future medical
developments. Equally important to the medical device industry is to
understand the risks to health and the regulatory concerns.
Definitions
The definitions of words beginning with nano
are not always clear-cut. For example, some descriptions of nanotechnology
are not really nano, dealing instead with structures on the micron scale
(one millionth of a meter), which is a thousand times larger than a
nanometer. In some cases, what is called nanotechnology isn’t
technology. Rather, it involves basic research on structures having at
least one dimension of about one to several hundred nanometers.1
To get a sense of the nanoscale, a human hair measures about a hundred
microns across, and a bacterial cell measures a few hundred nanometers.
Other definitions include
•
Nanomaterials: Materials designed and
produced to have structural features with at least one dimension of 100 nm
or less.
•
Nanoscale: Refers to phenomena that
occur on the length scale between 1 and 100 nm.
•
Nanoscience: A discipline involving
scientific understanding and investigation of nanoscale phenomena.
•
Nanostructures: Structures whose
characteristic variation in design length is at the nanoscale.
•
Nanotechnology: The application of
nanoscience in technological devices.
Fundamentals
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These optical microscope images of aligned osteoblast
demonstrate the alignment of carbon nanofibers after two days of
growth. Source: Purdue University. |
One nanometer is a magical point on the
dimensional scale. It is the length of a small molecule. By contrast,
atoms measure one-tenth of a nanometer. Nanostructures are at the
confluence of the smallest of man-made devices and the largest molecules
of living things.1 Nanotechnology is concerned with the shell
of the atom, the scale at which the new technology becomes a reality.
Making molecules that can organize
themselves on their own or with a supporting surface like metal or plastic
is a key strategy for manufacturing nanostructures.2
Nanotechnology and biology share many
similarities. The most complicated organisms are made up of tiny cells,
which are constructed from nanoscale building blocks: proteins, lipids,
nucleic acids, and other complex molecules.3 With
nanotechnology, tiny nanostructures are made from semiconductors, metals,
plastics, or glass.
At the nanoscale, materials behave
differently. Increased reactivity is one such difference; this property is
a function of the increased ratio of an object’s surface area to its
volume as it gets smaller. Silver, for example, performs differently at
the nanoscale. The increased reactivity of nanoparticles of silver is used
in infection control.
Because each tiny particle in a
nanostructure has its own surface area, it increases the overall surface
area of silver oxide, which means that more silver can interact in body
fluids to encounter and inhibit microbes.4 Gold becomes a good
catalyst for fuel cells at nanoscopic sizes and is being used in a number
of nanotechnology devices for medical purposes. Nanoscale building blocks
fabricated from 1-nm buckyballs made from carbon can be used as a scaffold
to repair damaged tissue and bone.1
Nanoparticles can be coated with other
substances, allowing materials of such composite particles to combine
several properties. One example is employing ceramic nanoparticles with
organic shells to reduce the surface tension of water and then using the
combination as an antifogging coating.2
Current
and Future Developments
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Hydroxyapatite crystal is grown on a coated nanotube surface.
Photo supplied by the University of California at Riverside. |
More than 60 drugs and drug-delivery systems
based on nanotechnology, and more than 90 medical devices or diagnostic
tests, are already being tested, according to NanoBiotech News, a weekly
newsletter that tracks advances in the field.5 One device
includes the use of quantum dots, bits of material so tiny that they are
often just a few atoms across. The dots are used as research tools to help
understand how proteins, DNA, and other biological molecules attach to
transport systems inside cells. Quantum dots are coated with a material
that makes them attach to specific target molecules that may be early
indicators of disease.
Clinical studies have begun to study an
adaptive retinal implant designed to restore partial vision in cases of
blindness caused by retinitis pigmentosa. The system includes a tiny
camera in the frame of eyeglasses. The camera transmits images of the
surroundings to a special adaptive signal processor.2
Developments in nanoscale biomedicine should
be able to create implants that release drugs on demand and monitor blood
chemistry. According to the European Commission, with nanotechnology,
nanoelectronics, and microsystem technology, complex analysis equipment
will become available that will be within the price range of the private
household.2 A tiny jab in the finger will be enough for future
blood analysis to measure cholesterol and glucose, and the results can be
e-mailed to the nearest nanomedical center for a more accurate diagnosis
and treatment.
Using
nanotechnology, the medication could
be carried in supramolecular hollow molecules, nanoscale transport
containers with antennas to which antibodies of similar sensory proteins
are attached. When the molecules come into contact with structures typical
of the agent responsible for the illness, they dock onto it and send a
signal to the hollow molecule, which opens up and releases its contents.2
With such nanotechnology, medications could be delivered in high doses
directly to the source of the illness, placing no stress on the rest of
the body and minimizing side effects.
In the United States, the National Cancer
Institute has committed to a new $144.3 million, five-year initiative to
develop and apply nanotechnology to cancer. According to the institute’s
former director and acting FDA commissioner Andrew von Eschenbach,
“Nanotechnology has the potential to radically increase our options for
prevention, diagnosis, and treatment of cancer.” He added that the
institute’s commitment to this cancer initiative comes at a critical
time and that nanotechnology supports and expands scientific advances in
genomics and proteomics while it builds on our understanding of the
molecular underpinning of cancer.6
One of the first nanoscale devices to show
promise in fighting cancer and administering drugs is a tiny construction
called a nanoshell. A nanoshell consists of beads that are about three
millionths of an inch wide, with an outer metal wall and an inner silicon
core. By varying the size ratio between the wall and core, scientists can
tune the shells precisely to absorb or scatter specific wavelengths of
light. Gold-encased nanoshells can convert these specific wavelengths of
light into heat.
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Microcapsules that could deliver drugs are small enough to pass
through living cells. Photo courtesy of Rice University. |
Selectively binding these shells to
malignant cells could provide a means for fighting cancer. Infrared rays
would pass harmlessly through soft tissue but generate lethal heat where
they strike the nanoshells. In laboratory tests, investigators have used
this selective heating to cook tumor cells without harming surrounding
healthy cells.3 Nanoshells may also be able to trigger
implanted temperature-sensitive drug-delivery devices, releasing a dose
only when illuminated with a specific infrared wavelength.
A key focus of nanotechnology researchers is
to develop new ways to seek out and destroy cancer cells. Nanoshells work
by cooking cells, but there are other methods. Ralph Weichselbaum, chief
of radiation oncology at the University of Chicago, and Vigi
Balasubramanian of the Illinois Institute of Technology are collaborating
on a project to incorporate a cancer-killer gene into a nanocapsule.
The gene elaborates tumor necrosis factor,
which, when injected in large doses, is toxic not only to cancer cells but
also to healthy cells. To avoid damage to normal tissue, the nanocapsule
is coated with sensors that zero in only on tumor cells. A patient would
then be exposed to low-dose radiation or drugs that trigger the gene to
make the necrosis factor.7 Nanoparticles are also capable of
passing through the blood-brain barrier filter system, so that they can be
used as specially coated magnetite particles that are warmed by an
alternating electromagnetic field to combat brain tumors.2
Nanosphere Inc. is developing molecular
testing systems that would enable detection of patient predisposition to
medical conditions and allow physicians to optimize patient drug response
based on genetic variations while simultaneously reducing the occurrence
of adverse drug reactions.8 The company has developed a system
using gold nanoparticles attached to strands of nucleotides complementary
to targets of interest such as the mecA gene, a biomarker associated with
clinically challenging methicillin-resistant Staphylococcus aureus. When a
target nucleic acid or protein is present, the nanoparticle probes latch
onto the match and provide an optical signal indicating that the target
has been found. The system is ready to adapt to a full range of targets as
soon as clinically relevant markers become available.
Risks
to Health
Although there are a number of promising
breakthroughs in medicine, relatively little is known about the potential
health and environmental effects of tiny particles. Millions of dollars
are being spent on product development, but some scientists feel that
insufficient funds are committed to determining whether nanomaterials pose
a danger to human health. It is recognized that subtle changes in the size
of the particles used in the nanoscale materials can precipitate widely
different changes in their properties, including their toxicity.
Laboratory studies, for example, have shown
that inhaled airborne nanoscale materials depositing in the respiratory
tract can cause an inflammatory response.9 The small size of
engineered nanomaterials also makes their uptake easier into and between
various cells, allowing for transport to sensitive target sites in the
body, including bone marrow, spleen, heart, and brain. In addition to
size, the shape, solubility, surface chemistry, and surface area of
ultrafine particles are known to increase inflammation and tissue damage.
These are not properties that are usually considered when evaluating
hazards and health effects.10
At a recent hearing presented to the U.S.
House of Representatives Committee on Science, the director of the Project
on Emerging Nanotechnologies, David Rejeski, described the current lack of
knowledge about nanotechnology-based products, possible health and
environmental implications, and the oversight process designed to manage
any potential risks that could breed U.S. public mistrust and suspicion.11
He pointed out that the technology is developing more rapidly than the
understanding of the environmental, health, and safety risks, and more
rapidly than the government’s ability to respond with effective policy
measures. Rejeski asked for a coordinated federal strategy, i.e., a nano
safety reporting system, and additional funding to address current and
future safety concerns, particularly since many nanotechnology-based
products, such as cosmetics and consumer products, are entering the market
in areas with little or no government oversight.
A recent seminal paper points out the strong
likelihood that biological activity of nanoparticles will depend on
physiochemical parameters not routinely considered in toxicity screening
studies.12 Because engineered nanomaterials show behavior that
depends on their physical and chemical structure, risk assessment
paradigms that have been developed based on traditional bulk chemistry
alone may no longer be valid. This same paper provides a comprehensive set
of principles for characterizing the potential human health effects from
exposure to nanomaterials. The paper can be used as a screening strategy
for risk assessment purposes. Oral, dermal, inhalation, and injection
routes of exposure are included, recognizing that, depending on use
patterns, exposure to nanomaterials may occur by any of these routes.
Regulatory
Issues
According to a recent review, nanotechnology
has three major uses in medicine.13 The first is delivering the
exact dose of a drug to the intended location. The second is providing new
ways to grow and repair body tissues; the third is using the detection of
single molecules in diagnosis. All of this means that new discoveries will
present many exciting challenges for regulatory affairs, clinical
research, and research and development personnel.
Becoming conversant with pharmacodynamics
and pharmacokinetics for recently marketed combination drugs and devices,
including those on the horizon, requires basic knowledge about physics,
chemistry, biochemistry, genetics, molecular biology, materials science
(i.e., nanomaterials), toxicology, bioinformatics, and engineering. In
addition, the toxicology and environmental effects, as they relate to
nanoparticles, will be extremely important issues for manufacturers.
Any of this information that is related to
the new delivery system or compound must be compiled, understood, and
lucidly explained in writing or, perhaps, verbally to agency reviewers
prior to gaining premarket approval.
References
1. M Ratner and D Ratner, Nanotechnology
(Upper Saddle River, NJ: Prentice Hall, 2003).
2.
Nanotechnology: Innovation for
Tomorrow’s World (Brussels: European Commission, 2004).
3. AP Alivisatos, “Less Is More in
Medicine,” Understanding Nanotechnology (New York: Warner Books, 2002),
56–69.
4. D Tobler and L Warner, “Nanotech Silver
Fights Microbes in Medical Devices,” Medical Device & Diagnostic
Industry 27, no. 5 (2005): 164–169.
5. R Weiss, “Nanomedicine’s Promise Is
Anything but Tiny,” Washington Post, January 30, 2005: A08.
6. NIH News, National Institutes of Health,
September 13, 2004.
7. R Kotulak, “Tiny Battlefield in the War
on Disease,” Chicago Tribune, September 14, 2004: 10.
8. “Technology Overview” [online];
available from Internet: www.nanosphere-inc.com/tech.
9. G Oberdorster et al., “Nanotoxicology:
An Emerging Discipline Evolving for Studies of Ultrafine Particles,”
Environmental Health Perspectives 113, no. 7 (2005): 823–839.
10. A Maynard and E Kuempel, “Airborne
Nanostructured Particles and Occupational Health,” Journal of
Nanoparticle Research 7 (2005): 587–614.
11. Testimony of David Rejeski, director,
Project of Emerging Nanotechnologies, before the U.S. House of
Representatives Committee on Science, November 17, 2005.
12. G Oberdorster et al., “Principles for
Characterizing Potential Human Health Effects from Exposure to
Nanomaterials: Elements of a Screening Strategy,” Particle and Fibre
Toxicology [online] October2005 [cited 5 April 2006]; available from
Internet: www.particleandfibretechnology. com/content/2/1/8.
13. T Delamothe, “Nanotechnology: Small
Science, Big Deal,” British Medical Journal 330, no. 5 (2005): 544.