Newswise — A nanoparticle-based drug delivery concept
in which an applied magnetic field directs the accumulation
in tumor cells of custom-designed, drug-filled nanocarriers
has been demonstrated by University at Buffalo researchers.
The new approach, recently published in Molecular
Pharmaceutics , may lead to treatments that
exploit the advantages of photodynamic therapy
(PDT) and that have the potential to reduce drug
accumulation in normal tissues.
The in vitro results showed that magnetically guided
delivery to tumor cells of these customized nanocarriers
allowed for more precise targeting, while boosting
cellular uptake of the PDT drugs contained inside
them.
"This is a novel way to enhance drug delivery to
cells," said Paras Prasad, Ph.D., executive director
of UB's Institute for Lasers, Photonics and Biophotonics,
SUNY Distinguished Professor in the Department of
Chemistry in the UB College of Arts and Sciences
and co-author on the paper.
"The externally applied magnetic field acted as
a kind of 'remote control,' directing the nanocarriers
to the targeted area in the cell culture," he said.
Once the magnetic field was applied, the concentration
of drug inside the tumor cells in the target area
increased.
"We have shown that we can use magnetophoretic control
to deliver PDT drug to tumor cells, resulting in
increased accumulation inside those cells," explained
Tymish Ohulchanskyy, Ph.D., senior research scientist
in the Department of Chemistry.
The research was conducted with partial funding
from UB's New York State Center of Excellence in
Bioinformatics and Life Sciences, which is a major
supporter of the nanomedicine program at the Institute
for Lasers, Photonics and Biophotonics. Prasad is
affiliated with the Bioengineering/Tissue Engineering
Team at the Center of Excellence.
"The nanomedicine work by Dr. Prasad and his team
has far-reaching implications for a variety of disease
areas, including neurological disease and cardiac
disease," said Bruce A. Holm, UB senior vice provost
and executive director of the Center of Excellence. "The
institute represents a key partner with the Center
of Excellence."
According to Prasad, photodynamic therapy is one
of the most promising treatments for cancer; it's
also being investigated as a treatment method for
cardiovascular, dermatological and ophthalmic diseases.
PDT exploits the propensity of tumors to retain
higher concentrations of photosensitive drugs than
normal tissues. When exposed to laser light, these
drugs generate toxic molecules that destroy the cancer
cells.
The main side effect associated with photodynamic
cancer therapy is the patient's strong sensitivity
to light for four to six weeks after treatment, a
result of PDT drugs that accumulate in the skin.
"The magnetically guided drug delivery would allow
for the use of lower concentrations of the drug to
deliver a therapeutic dose, thus significantly reducing
the amount of PDT drug that accumulates in normal
tissue," said Prasad.
The UB team achieved these results with a novel
nanocarrier system, developed from polymer micelles,
which are nanosized, water-dispersible clusters of
polymeric molecules.
Prasad explained that polymeric micelles are excellent
nanocarriers for PDT drugs, which are mostly water-insoluble.
Along with the photodynamic drug, the UB researchers
encapsulated inside the nanocarriers iron oxide nanoparticles,
which allowed them to respond to externally applied
magnetic fields.
In the experiments, nanocarriers were shown to be
efficiently taken up by cultured tumor cells in the
area exposed to the magnetic field, as demonstrated
by confocal microscopy.
While the team has demonstrated this concept with
PDT drugs, Prasad said the technique would be useful
in delivering gene therapy, chemotherapy or practically
any kind of pharmaceutical treatment into cells.
"Because the nanocarriers proved to be significantly
stable and because they retained the PDT drugs, we
are optimistic that they will be able to deliver
a wide range of therapies to tumors or other disease
sites in the body without any significant loss in
the circulatory system or in normal tissues," said
Prasad.
The team is beginning in vivo studies on the new
drug-delivery method.
Preliminary studies in live animals have indicated
that an applied magnetic field can effect a localized
accumulation in the tumor site, according to Earl
J. Bergey, Ph.D., deputy director of biophotonics
at the UB institute and a co-author on the paper.
Other co-authors are Ludmila O. Cinteza, Ph.D.,
former post-doctoral researcher at the institute;
Ravindra K. Pandey, Ph.D., professor of biophysical
sciences at the Roswell Park Cancer Institute and
research professor at the institute and Yudhisthira
Sahoo, Ph.D., research assistant professor in the
UB Department of Chemistry.
The UB research was funded by the John R. Oishei
Foundation, UB's New York State Center of Excellence
in Bioinformatics and Life Sciences and by the UB
Interdisciplinary Research and Creative Activities
Fund. New York State Sen. Mary Lou Rath also has
provided generous support to UB's Institute for Lasers,
Photonics and Biophotonics.
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