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UNC study:
shape, not just size, impacts effectiveness of emerging
nanomedicine therapies
Other Topics:
Nanotech Textile Plant
University of North Carolina at Chapel Hill
August 4, 2008
Chapel Hill, NC -– In the budding field of nanotechnology,
scientists already know that size does matter.
But now, researchers at the University of North Carolina at
Chapel Hill have shown that shape matters even more — a
finding that could lead to new and more effective methods
for treating cancer and other diseases, from diabetes and
multiple sclerosis to arthritis and obesity. |
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A team of researchers led by Joseph DeSimone,
Ph.D., Chancellor's Eminent Professor of Chemistry in UNC's
College of Arts and Sciences and William R. Kenan, Jr.
Distinguished Professor of Chemical Engineering at North
Carolina State University, and Stephanie Gratton, a graduate
student in DeSimone's lab, have demonstrated that
nanoparticles designed with a specific shape, size and
surface chemistry are taken up into cells and behave
differently within cells depending on these attributes.
Their findings appear in this week's online early edition of
the journal PNAS, the Proceedings of the National Academy of
Sciences.
Using nanoparticles to combat cancer is an area of interest
for many researchers. For decades, treating the disease has
mostly involved injecting patients with toxic drugs – a
practice in which only a fraction of the drugs reach the
intended target, killing healthy cells in the process and
causing harmful side effects.
Previous studies have shown that drug-carrying nanoparticles
can hone-in on and attack tumors, in part because of their
extremely small size — less than 100 nanometers (one
nanometer = one billionth of a meter) — which helps allow
them to pass through cell membranes. However, up until now,
existing techniques have meant that targeting agents could
only be delivered using spherical or granular shaped
particles.
Using PRINT® (Particle Replication in Non-wetting Templates)
technology — a technique invented in DeSimone's lab that
allows scientists to design and produce "custom-made"
nanoparticles — the UNC researchers made particles with
specific shapes, sizes and surface charges. DeSimone said
the aim is to optimize particle attributes for specific
therapeutic objectives.
"This would mean that we could deliver lower dosages of
drugs to specific cells and tissues in the body and actually
be more effective in treating the cancer," said DeSimone,
who is also a member of UNC's Lineberger Comprehensive
Cancer Center and the co-principal investigator for the
Carolina Center for Cancer Nanotechnology Excellence.
Creating particles of different dimensions, the UNC
researchers changed one variable at a time, and experimented
with different surface chemistries. They then incubated the
different particles with human cervical carcinoma epithelial
(HeLa) cells, monitoring each type to see which ones the
cells absorbed most effectively.
For instance, the scientists discovered that long,
rod-shaped particles (diameter, 150 nanometers; height, 450
nanometers) were internalized by cells approximately four
times faster than lower aspect ratio particles (diameter,
200 nanometers; height, 200 nanometers), and traveled
significantly further into the cells as well.
Gratton noted the same phenomenon is found in natural
organisms.
"The long rod-shaped structure of bacteria may help explain
why PRINT® particles of higher aspect ratios are
internalized more rapidly and effectively than lower aspect
ratio particles," she said. "If we can design particles that
rely on the same mechanisms that nature has perfected for
bacteria, we may unlock the key for delivering therapeutics
more efficiently and effectively to treat and cure disease."
Liquidia Technologies, a UNC spin-off company, has an
exclusive license to the PRINT® technology and is developing
engineered nanoparticles for delivery of nucleic acids and
small molecule therapeutics. Liquidia also sponsors research
in the DeSimone lab. The company's chief executive officer,
Neal Fowler, said the study's findings should prove of
interest to the biopharmaceutical industry.
"We are delighted to contribute to the important work that
Professor DeSimone and his students are undertaking in the
field of nanomedicine. This work answers key questions about
the role of particle shape and size that industry leaders
have been asking for some time," Fowler said.
The study was funded by the National Science Foundation, the
National Institutes for Health, the Carolina Center for
Cancer Nanotechnology Excellence, the William R. Kenan
Professorship and Liquidia Technologies.
Other UNC researchers who contributed to the study are
Patricia Ropp, Ph.D., Patrick Pohlhaus, Ph.D., Christopher
Luft, Ph.D. and Mary Napier, Ph.D., from the chemistry
department and the Carolina Center for Cancer Nanotechnology
Excellence, along with Victoria Madden, Ph.D., from the
School of Medicine's pathology department.
The Carolina Center for Cancer Nanotechnology Excellence is
part of the NCI Alliance for Nanotechnology in Cancer, a
comprehensive initiative designed to accelerate the
application of nanotechnology to the prevention, diagnosis
and treatment of cancer. To learn more about the program, go
to http://nano.cancer.gov/. |
