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Senior Citizen Health & Medicine
Nanotechnology Enables Low-Dose of Drug to Attack
Artery-Clogging Plaques
First time that nanoparticles deliver a drug to
disease site in a living organism
July 27, 2006 For many senior citizens the word
"nanotechnology" probably sounds like something out of Star Wars, which,
however, is also a little new for many seniors. But, nanotechnology will
most likely have a profound impact of the lives of many of people as they
face the challenges of aging. A good example is new information on a
laboratory test where one very low dose of a drug was enough to show an
effect on notoriously tenacious artery-clogging plaques. What kind of
drug is that potent?
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It's not so much the drug itself as how it was
delivered. Fumagillin -- a drug that can inhibit the growth of new blood
vessels that feed atherosclerotic plaques -- was sent directly to the
base of plaques by microscopically small spheres called nanoparticles
developed by researchers at Washington University School of Medicine in
St. Louis.
"Previously we reported that we can visualize
plaques using our nanoparticle technology, but this is the first time
we've demonstrated that the nanoparticles can also deliver a drug to a
disease site in a living organism," says Patrick Winter, Ph.D., research
assistant professor of medicine. "After a single dose in laboratory
rabbits, fumagillin nanoparticles markedly reduced the growth of new
blood vessels that feed plaques."
The researchers report their findings in the
September issue of the journal Arteriosclerosis, Thrombosis, and
Vascular Biology, and the article is now available on line.
An atherosclerosis plaque results when a buildup of
cholesterol, inflammatory cells and fibrous tissue forms inside an
artery. If a plaque ruptures, it can block blood flow to the heart or
brain, causing heart attack or stroke.
While growing, plaques require an influx of
nutrients, fats and cells, so they develop their own blood supply --
minute blood vessels that grow within the wall of arteries and penetrate
the plaque. Many believe that cutting off this blood supply could
stabilize or reduce plaques. In previous studies, fumagillin has been
shown to be an effective agent for stopping the process that creates new
blood vessels.
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What is Nanotechnology? |
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Nanotechnology is
the understanding and control of matter at dimensions of roughly
1 to 100 nanometers, where unique phenomena enable novel
applications. Encompassing nanoscale science, engineering and
technology, nanotechnology involves imaging, measuring,
modeling, and manipulating matter at this length scale.
At the nanoscale, the physical, chemical,
and biological properties of materials differ in fundamental and
valuable ways from the properties of individual atoms and
molecules or bulk matter. Nanotechnology R&D is directed toward
understanding and creating improved materials, devices, and
systems that exploit these new properties.
One area of nanotechnology R&D is
medicine. Medical researchers work at
the micro- and nano-scales to develop new drug delivery methods,
therapeutics and pharmaceuticals. For a bit of perspective, the
diameter of DNA, our genetic material, is in the 2.5 nanometer
range, while red blood cells are approximately 2.5 micrometers.
Additional information about
nanoscale research in medicine is available from the
National Institutes of Health.
A nanometer is one-billionth of a meter;
a sheet of paper is about 100,000 nanometers thick. See
The Scale of Things for a comparative view of the
sizes of commonly known items and nanoscale particles.
>>
For more on the National Nanotechnology Initiative click
here. |
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Riding on the nanoparticles, fumagillin is carried
to the site of new blood vessel formation and stays there thanks to a
fellow nanoparticle passenger -- a component that fastens the
nanoparticles to cells found in newly developing blood vessels. Stuck in
this position, the nanoparticle drops its load of fumagillin,
concentrating it at the site of the atherosclerotic plaque.
In this study, the single dosage of fumagillin each
rabbit received was 50,000 times lower than the total fumagillin dose
used in an earlier experiment by another research group and yet reduced
the growth of new blood vessels in plaques by 60 to 80 percent.
"Fumagillin can have neurocognitive side effects,
causing injury to the brain at high doses," Winter says. "The ability of
the nanoparticles to concentrate the drug at the disease site allows the
dose to be lowered. This could open the door for a lot of drugs that
have failed to be approved because they caused too many side effects at
a higher dose. It might pay to look at these drugs again and ask if
placing them on these nanoparticles can help them be effective at a
lower dose and clinically useful."
The nanoparticles are the invention of Samuel
Wickline, M.D., professor of medicine, of biomedical engineering, of
physics and of cell biology and physiology, and Gregory Lanza, M.D.,
Ph.D., associate professor of medicine and biomedical engineering. Both
are heart specialists at Barnes-Jewish Hospital.
The microscopic spheres are capable of carrying a
variety of components at the same time and can be detected with standard
MRI scans, making them useful for imaging disease sites while
simultaneously treating them. Using the nanoparticles, a physician can
confirm a drug has reached the desired location, measure the amount of
drug at the site, and later check to see if the drug has affected the
disease.
In the current study, the researchers fed rabbits a
high-cholesterol diet for 80 days before treatment with fumagillin
nanoparticles. The diet caused numerous small plaques in the rabbits'
aortas, but the plaques were considered to be at an early stage of
growth. By demonstrating the utility of the nanoparticles for early
intervention of atherosclerosis, the research group hopes that they can
help alleviate the need for more invasive treatment of later-stage
atherosclerosis.
"We wanted to go after the early stages of the
disease when patients don't yet need immediate intervention to prevent
serious cardiac problems," Winter says. "We think fumagillin
nanoparticles potentially could be incorporated into a protocol that
includes lipid-lowering statin drugs or dietary changes."
Next, the research group plans to study the effect
of fumagillin nanoparticles in the treatment of cancerous tumors.
According to Winter, the use of inhibitors of blood vessel growth is a
well-accepted therapy for cancer, suggesting the nanotechnology may
prove beneficial in cancer therapy.
Winter PM, Neubauer AM, Caruthers SD, Harris TD,
Robertson JD, Williams TA, Schmieder AH, Hu G, Allen JS, Lacy EK,
Wickline SA, Lanza GM. Endothelial ανβ3 integrin-targeted fumagillin
nanoparticles inhibit angiogenesis in atherosclerosis. Arteriosclerosis,
Thrombosis, and Vascular Biology September 2006, available on line ahead
of print.
Notes:
Funding from the National Institutes of Health, the
American Heart Association and Philips Medical Systems supported this
research.
Washington University School of Medicine's
full-time and volunteer faculty physicians also are the medical staff of
Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine
is one of the leading medical research, teaching and patient care
institutions in the nation, currently ranked fourth in the nation by
U.S. News & World Report. Through its affiliations with Barnes-Jewish
and St. Louis Children's hospitals, the School of Medicine is linked to
BJC HealthCare.
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