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Nanotech researchers' two-step method shows promise in fighting pancreatic cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer that uses two different types of nanoparticles, the first type clearing a path into tumor cells for the second, which delivers chemotherapy drugs.
The research team, led by Dr. Andre Nel, a UCLA professor of
nanomedicine and a member of the California NanoSystems
Institute at UCLA, and Dr. Huan Meng, a UCLA adjunct assistant
professor of nanomedicine, has shown that this new drug-delivery
technique is effective in treating pancreatic cancer in a mouse
model.
The results of the study are published online in the
journal ACS Nano and will be featured in the November
2013 print issue.
Pancreatic ductal adenocarcinoma, or pancreatic
cancer, is a deadly disease that is nearly
impossible to detect until it is in the advanced
stage. Treatment options are limited and have
low success rates. The need for innovative and
improved treatment of pancreatic cancer cannot
be overstated, the researchers said, as a
pancreatic cancer diagnosis has often been
synonymous with a death sentence.
Pancreatic ductal adenocarcinoma tumors
are made up of cancer cells that are
surrounded by other structural elements
called stroma. The stroma can be made of
many substances, including connective
tissue and pericyte cells, which block
standard chemotherapy drugs in tumor
blood vessels from efficiently reaching
the cancer cells, reducing the
effectiveness of treatment.
The dual-wave nanotherapy method
employed by Nel and Meng uses
two different kinds of
nanoparticles injected
intravenously in a rapid
succession. The first wave of
nanoparticles carries a
substance that removes the
pericytes' vascular gates,
opening up access to the
pancreatic cancer cells; the
second wave carries the
chemotherapy drug that kills the
cancer cells.
Nel and Meng, along with
colleagues Dr. Jeffrey
Zink, a UCLA professor
of chemistry and
biochemistry, and Dr.
Jeffrey Brinker, a
University of New Mexico
professor of chemical
and nuclear engineering,
sought to place
chemotherapy drugs into
nanoparticles that could
more directly target
pancreatic cancer cells,
but they first needed to
find a way to get those
nanoparticles through
the sites of vascular
obstruction caused by
pericytes, which
restrict access to the
cancer cells.
Through
experimentation,
they discovered
they could
interfere with a
cellular
signaling
pathway — the
communication
mechanism
between cells —
that governs the
pericytes'
attraction to
the tumor blood
vessels. By
creating
nanoparticles
that effectively
bind a high load
of the signaling
pathway
inhibitor, the
researchers were
able to develop
a first wave of
nanoparticles
that would
separate the
pericytes from
the endothelial
cells on the
blood vessel.
This would open
the vascular
gate for the
next wave of
nanoparticles,
which carry the
chemotherapeutic
agent to the
cancer cells
inside the
tumor.
To test
this
nanotherapy,
the
researchers
used
immuno-compromised
mice in
which
they
grew
human
pancreatic
tumors
called
xenografts
under
the
skin.
With the
two-wave
method,
the
xenograft
tumors
had a
significantly
higher
rate of
shrinkage
than
tumors
exposed
only to
chemotherapy
given as
a free
drug or
carried
in
nanoparticles
without
first-wave
treatment.
"This two-wave nanotherapy is an existing example of how we seek to improve the delivery of chemotherapy drugs to their intended targets using nanotechnology to provide an engineered approach," said Nel, chief of UCLA's division of nanomedicine. "It shows how the physical and chemical principles of nanotechnology can be integrated with the biological sciences to help cancer patients by increasing the effectiveness of chemotherapy while also reducing side effects and toxicity. This two-wave treatment approach can also address biological impediments in nanotherapies for other types of cancer."
The research was funded by the U.S. Public Health Service and the National Cancer Institute.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2013, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 14 consecutive years.
UCLA; November 14, 2013
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