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The World of Nanotechnology
Max Sherman, RPh
Sherman Consulting Services
Warsaw, Indiana
US Pharm. 2004;12:HS-3-HS-4.
There have been many changes in the science of drug discovery in the past decade. One
advance that stands out, for example, is employing a patient's genetic profile to judge whether or
not a specific drug will be effective in treating disease. Decoding the human genome spawned
"pharmacogenomics." This term was applied in the late 1950s, first to understand the genetic
differences that cause people to metabolize drugs differently, and then to describe the creation
of drugs in the 1990s that are individually designed for a person's genetic makeup. Genetic
testing is now used to identify breast cancer patients who might benefit from therapy with
Herceptin (trastuzumab), a monoclonal antibody. The drug targets cancer cells that overexpress
a protein called HER-2, which is found on the surface of cancer cells. In tumor cells, errors in
DNA replication may result in multiple copies of a gene on a single chromosome. This alteration,
known as gene amplification, leads to an overexpression of the HER-2 protein, resulting in
increased cell division and a higher rate of cell growth. Herceptin is used only to treat cancers
that overexpress the HER-2 protein.1 The 21st century will no doubt be witness to a number of
new discoveries in this field as scientists continue to solve the riddles of human genomics.
Precise genetic testing will be pivotal in employing new monoclonal antibodies and other new
drug therapies.
The Science of Nanotechnology
Science is learning more about the human body on a smaller and smaller scale. The next wave
of drug discovery will likely focus on nanotechnology. We will in fact be seeing more and more
scientific terms beginning with nano. Nanoscience has been deemed the technology
breakthrough of tomorrow, and several research groups are developing programmable implants
that could revolutionize the way drugs are made and administered. Nanoparticles could be used
to deliver chemotherapeutic agents exactly where they are needed, preventing the side effects
that so often result from potent medicines. Artificial nanoscale building blocks may one day be
used to help repair tissues such as skin, cartilage, and bone.2 According to one expert in the
field, nanomedicine will have extraordinary and far-reaching implications for the medical
profession, for the definition of disease, and for the diagnosis and treatment of medical
conditions, including aging.3 Before embarking on some of the aspects of nanotechnology it is
prudent to include a few definitions.
Defining the World of Nanotechnology
The prefix nano- is a Greek term meaning one billionth.
One nanometer (abbreviated as 1 nm) is 1/1,000,000,000
of a meter. To get a sense of the nano scale, consider
that a human hair measures 50,000 nanometers across; a
bacterial cell, a few hundred nanometers. The smallest
objects visible with the unaided human eye are 10,000
nanometers across.4
Nanoscience is the study of the fundamental principles of
molecules and structures with at least one dimension
roughly between 1 and 100 nanometers. These structures
are appropriately termed nanostructures. Nano-structures
are the smallest solid things possible to make and are
described as being at the confluence of the smallest of
human-made devices and the largest molecules of living
things.
Nanotechnology is the application of these nanostructures
into useful nanoscale devices.
Nanoscale is the natural scale of all fundamental life
processes, and it is the scale at which diseases need to
be met and conquered.
Molecular nanotechnology has been defined as the threedimensional positional control of molecular structure to
create materials and devices to molecular precision.
Nanomedicine is the science designed to employ
molecular machine systems to address medical problems.
It uses molecular knowledge to maintain and improve
human health at the molecular scale, the scale "on which
all living cells, and the things that nourish or kill them,
operate," according to a report in the New York Times.10
Mechanism of action: Nanotechnology and biology share many similarities. The most
complicated organisms are made up of tiny cells that are constructed from nanoscale building
blocks: proteins, lipids, nucleic acids, and other complex biological molecules. 2 Nano-technology
utilizes tiny nanostructures made from semiconductors, metals, plastic, or glass. Inorganic
structures of nanometer scale have already been commercialized as contrast agents.
Drug development is a nanoscale activity. Some of the largest and most important categories of
drugs are those that work by interacting specifically with DNA or proteins in the body. This class
of drug molecules includes aspirin, cisplatin, and other anticancer agents, together with much
more complex molecules like beta-blockers, anti-inflammatory agents, antidepressants, and
compounds used in AIDS therapy.4
Controlled Drug Delivery
The major requirement for implantable drug delivery devices is controlled release of therapeutic
agents as a continuous process over an extended period of time. The goal is to achieve a
continuous drug release profile consistent with zero-order kinetics where the concentration of the
drug remains constant throughout the delivery period.5 Pharmacists are aware that most
injectable drugs display first-order kinetics, in that there is an initially high concentration in
plasma, followed by an exponential fall in concentration. Toxicity can occur when the peak
concentration is above the therapeutic range, while drug efficacy diminishes as the drug
concentration falls below this range. Drug delivery systems with a zero-order release rate have
several potential therapeutic advantages, including in vivo predictability of release rate on the
basis of in vitro data; minimized peak plasma levels and reduced risk of adverse reactions;
predictable and extended duration of action; reduced inconvenience of frequent redosing; and
improved patient compliance.5 Controlled drug delivery should thus be aimed at improved drug
treatment outcomes through rate- and time-programmed and site-specific targeting.6
Nanotechnology now provides the means to achieve this goal. New technologies like molecular
modeling, combinatorial chemistry, high throughput screening, and bioinformatics are the
engineering tools of the future. According to one researcher, "Future categories of medicinal
treatment will comprise the following: mechanism-based small molecules (with several new
classes of medicines), therapeutic proteins and other macromolecules, gene regulating
medicines and gene therapy."6
Current and Future Developments
Developments in nanoscale biomedicine should be able to create implants to release drugs on
demand and to monitor blood chemistry. This has been recognized by the National Cancer
Institute (NCI). The NCI has committed to a new $144.3 million, five-year initiative to develop
and apply nanotechnology to cancer. According to NCI's director, Dr. Andrew von Eschenbach,
"Nanotechnology has the potential to radically increase our options for prevention, diagnosis,
and treatment of cancer." He also added that NCI's commitment to this cancer initiative comes at
a critical time and that nano-technology supports and expands the scientific advances in
genomics and proteomics while it builds on our understanding of the molecular underpinning of
cancer.7
Among the first nanoscale devices to show promise in fighting cancer and administering drugs
are tiny constructions called nanoshells. These devices consist of beads which 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 forms of light into heat.
There is thus a possibility to fight cancer by selectively binding these shells to malignant cells.
Infrared rays would pass harmlessly through soft tissue but generate lethal heat where they
strike the nanoshells. In laboratory tests, the investigators have used this selective heating to
"cook" tumor cells without harming surrounding healthy ones.2 Nanoshells may also be able to
trigger implanted, temperature-sensitive drug delivery devices, releasing a dose only when
illuminated with a specific infrared wavelength.
One company, Nanosphere Incorporated, is developing molecular testing systems to enable
doctors to detect patient predisposition to medical conditions and to allow them 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.
NanoHorizons, State College, PA, has begun to sell a line of metallic nanoparticles that are
compatible with standard polymer manufacturing processes. This means that silver, gold, and
other materials that kill bacteria and odor-causing microbes can be incorporated into shoes,
athletic equipment, and other plastic or nylon products. The materials can be made into particles
shaped like rods or spheres that are designed to greatly increase the available surface area of
the metal. Thus far less material is needed to achieve the same results that layers of ordinary
bulk metals would achieve. The company claims that its particles are 20 to 100 times more
efficacious in killing bacteria than similar metals in bulk form. NanoHorizons has also developed
nanoscale materials and devices for drug development research. They would be used with mass
spectrometry to screen potential drug combinatorial chemistry products and for general small
molecule identification. Biophan Technologies Inc. is another company immersed in
nanotechnology. Their strategy is to develop a method of bonding drugs to nanomagnetic
materials which respond to externally applied magnetic fields. The drug would be incorporated
into a polymer coating and used to treat solid tumors. Magnetic fields would be used to
concentrate the drug particles at the tumor site, and modulating the fields would release the drug
from the coating to attack cancer cells. Biophan is also using nanotechnology to enhance MRI
visualization by developing novel contrast materials to replace gadolinium. These new materials
would enhance signal intensity, be less toxic, and be chemically stable. According to the
company, nanomagnetic technology will provide materials for controlled drug delivery by
directing carriers to a specific location with magnetic fields, which is verified by MRI, and then
activated on demand in a limited region.
One of the top goals of researchers is to develop new ways to seek out and destroy cancer cells.
Nanoshells work by "cooking" cells, but there are other methods. Dr. Ralph Weichselbaum,
Chief of Radiation Oncology at the University of Chicago, and Viji 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 is toxic not only to cancer cells
but also to healthy cells when injected in large doses. 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. 9
A New Curriculum for Pharmacy Schools
Burgeoning new discoveries have made the last few years an interesting, exciting, and
challenging time for all in pharmacy and related health care. Understanding how drugs work at
the molecular level, genetic variations, gene sequences, gene therapy, biomarkers, proteomics,
pharmacogenomics, the role of enzyme systems in drug metabolism, and now nanotechnology
have added new material to the curriculum at schools of pharmacy and to continuing education
programs. Becoming conversant with pharmacodynamics and pharmacokinetics for recently
marketed drugs and those on the horizon will require an in-depth knowledge of physics,
chemistry, biochemistry, genetics, molecular biology, material science, bioinformatics, and
engineering. Additionally, it is arguably most important to consider how to assimilate and
disseminate relevant information about these new technology breakthroughs to patients and
health care professionals and to do it accurately, clearly, simply, and briefly–not an easy task for
today's and future pharmacists.
To comment on this article, contact [email protected].
REFERENCES
1. Cancer Facts, National Cancer Institute, http://cis.nci.nih.gov. Feb. 14, 2002.
2. Alivisatos AP. Less is more in medicine. In Understanding Nanotechnology, Warner Books,
New York, 2002, pg 56-69.
3. Freitas RA. Nanomedicine Vol. 1: Basic Capabilities–A Review. Landes Bioscience;
Georgetown, TX, 1999.
4. Ratner M, Ratner D. Nanotechnology, Prentice Hall, Upper Saddle River, NJ, 2003.
5. Sinha PM, et al. Nanoengineered device for drug delivery application. Nanotechnology
15:S585-589, 2004.
6. Breimer DD. Future challenges for drug delivery. Controlled Release 62:3-6, 1999.
7. NIH News, National Institutes of Health, Monday, September 13, 2004.
8. www.nanosphere-inc.com.
9. Kotulak R. Tiny battlefield in the war on disease. Chicago Tribune, September 14, 2004.
10. Feder BJ. Doctors use nanotechnology to improve health care. New York Times, November
1, 2004.
Vol. No: 29:12 Posted: 12/15/04