Nano-Sized Technology Has Super-Sized Effect on
Slowing Tumor Growth
Researchers find success with 1,000 times lower
dose of chemotherapy
A tumor treated with fumagillin nanoparticles
(left) is smaller than an untreated tumor. Nanoparticles containing an
image-enhancing metal (yellow) show that the treated tumor has much less
blood vessel growth than the untreated tumor.
April 2, 2008 - In the world that most senior citizens live in,
discussions frequently turn to cancer treatments, since contemporaries are
often battling the disease. The struggle against the
side-effects of chemotherapy frequently comes up. There is good news
today, however, that researchers may have found a way to use
nanotechnology to dramatically reduce the dose of chemo required.
Researchers at Washington University School of
Medicine in St. Louis focused a powerful drug directly on tumors in
rabbits using drug-coated nanoparticles. They found that a drug dose
1,000 times lower than used previously for this purpose markedly slowed
tumor growth.
"Many chemotherapeutic drugs have unwanted side
effects, and we've shown that our nanoparticle technology has the
potential to increase drug effectiveness and decrease drug dose to
alleviate harmful side effects," says lead author Patrick M. Winter,
Ph.D., research assistant professor of medicine and biomedical
engineering.
The nanoparticles are extremely tiny beads of an
inert, oily compound that can be coated with a wide variety of active
substances. In an article published online in The FASEB Journal, the
researchers describe a significant reduction of tumor growth in rabbits
that were treated with nanoparticles coated with a fungal toxin called
fumagillin. Human clinical trials have shown that fumagillin can be an
effective cancer treatment in combination with other anticancer drugs.
In addition to fumagillin, the nanoparticles'
surfaces held molecules designed to stick to proteins found primarily on
the cells of growing blood vessels. So the nanoparticles latched on to
sites of blood vessel proliferation and released their fumagillin load
into blood vessel cells. Fumagillin blocks multiplication of blood
vessel cells, so it inhibited tumors from expanding their blood supply
and slowed their growth.
Human trials have also shown that fumagillin can
have neurotoxic side effects at the high doses required when given by
standard methods. But the fumagillin nanoparticles were effective in
very low doses because they concentrate where tumors create new blood
vessels. The rabbits that received fumagillin nanoparticles showed no
adverse side effects.
Senior author Gregory M. Lanza, M.D., Ph.D.,
associate professor of medicine and of biomedical engineering, and
Samuel A. Wickline, M.D., professor of medicine, of physics and of
biomedical engineering, are co-inventors of the nanoparticle technology.
The nanoparticles measure only about 200 nanometers
across, or 500 times smaller than the width of a human hair. Their cores
are composed mostly of perfluorocarbon, a safe compound used in
artificial blood.
The nanoparticles can be adapted to many different
medical applications. In addition to carrying drugs to targeted
locations, they can be manufactured to highlight specific targets in
magnetic resonance imaging (MRI), nuclear imaging, CT scanning and
ultrasound imaging.
In this study, researchers loaded
blood-vessel-targeted nanoparticles with MRI contrast agent and were
able to make detailed maps of tumor blood vessel growth using standard
MRI equipment. The MRI scans showed that blood vessel formation tended
to concentrate in limited areas on the surface at one side of tumors
instead of dispersing uniformly, which was a surprise.
"Using the blood-vessel targeted nanoparticles, we
get a far more complete view of tumor biology than we would get with any
other technique," Winter says.
"If you followed a tumor over a period of time with
the nanoparticles and MRI scans, you would have a much better
understanding of the tumor's reaction to treatment."
The researchers say they believe nanoparticle
technology will be very useful for monitoring cancer treatment results
in both the short and long term.
"It gives you a way of determining whether you
should continue treatment, change the dose or even try a different
treatment altogether," Lanza says.
Prior work has shown that the nanoparticles can be
loaded with many kinds of drugs. The researchers used fumagillin
nanoparticles in these experiments to demonstrate the feasibility of
this approach, but they plan further investigations with other versions
of the nanoparticles.
"What this report clearly demonstrates is that our
nanoparticles can carry chemotherapeutic drugs specifically to tumors
and have an effect at the tumor site," Lanza says. "Sometimes when I
give presentations about our nanotechnology, people react as if it was
science fiction or at best a technology of the distant future. But we've
shown that the technology is ready for medical applications now."
The nanoparticles will be tested this year in
preliminary human clinical trials to determine the optimal method for
using them as imaging agents. These studies will lay essential
groundwork for using the nanoparticles as therapeutic agents.
Winter PM, Schmieder, AH, Caruthers SD, Keene JL,
Zhang H, Wickline SA, Lanza GM. Minute dosages of αvβ3-targeted
fumagillin nanoparticles impair Vx-2 tumor angiogenesis and development
in rabbits. The FASEB Journal. March 24, 2008 (advance online
publication).
The nanotechnology is owned by Barnes-Jewish
Hospital and Washington University and licensed to Kereos Inc, a St.
Louis-based company. Gregory M. Lanza and Samuel A. Wickline are
scientific cofounders of Kereos.
Funding from the National Cancer Institute, the
National Heart, Lung, and Blood Institute, the National Institute for
Biomedical Imaging and Bioengineering, Philips Medical Systems and
Philips Research supported this research.
Washington University School of Medicine's 2,100
employed 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 third 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.
Keep up with the latest news for senior citizens, baby
bommers
