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LA JOLLA, Calif., June 10, 2013 — Conventional treatments for diseases such as
cancer can carry harmful side effects—and the primary reason is that such
treatments are not targeted specifically to the cells of the body where they’re
needed. What if drugs for cancer, cardiovascular disease, and other diseases can
be targeted specifically and only to cells that need the medicine, and leave
normal tissues untouched?
A new study involving Sanford---Burnham Medical Research Institute’s Erkki
Ruoslahti, M.D., Ph.D., contributing to work by Samir Mitragotri, Ph.D., at the
University of California, Santa Barbara, found that the shape of nanoparticles can
enhance drug targeting. The study, published in Proceedings of the National
Academy of Sciences, found that rod---shaped nanoparticles—or nanorods—as
opposed to spherical nanoparticles, appear to adhere more effectively to the
surface of endothelial cells that line the inside of blood vessels.
“While nanoparticle shape has been shown to impact cellular uptake, the latest
study shows that specific tissues can be targeted by controlling the shape of
nanoparticles. Keeping the material, volume, and the targeting antibody the
same, a simple change in the shape of the nanoparticle enhances its ability to
target specific tissues,” said Mitragotri.
“The elongated particles are more effective,” added Ruoslahti. “Presumably the
reason is that if you have a spherical particle and it has binding sites on it, the
curvature of the sphere allows only so many of those binding sites to interact
with membrane receptors on the surface of a cell.”
In contrast, the elongated nanorods have a larger surface area that is in contact
with the surface of the endothelial cells. More of the antibodies that coat the
nanorod can therefore bind receptors on the surface of endothelial cells, and that
leads to more effective cell adhesion and more effective drug delivery.
Testing targeted nanoparticles
Mitragotri’s lab tested the efficacy of rod---shaped nanoparticles in synthesized
networks of channels called “synthetic microvascular networks,” or SMNs, that
mimic conditions inside blood vessels. The nanoparticles were also tested in vivo
in animal models, and separately in mathematical models.
The researchers also found that nanorods targeted to lung tissue in mice
accumulated at a rate that was two---fold over nanospheres engineered with the
same targeting antibody. Also, enhanced targeting of nanorods was seen in
endothelial cells in the brain, which has historically been a challenging organ to
target with drugs.
Nanoparticles already used in some cancer drugs
Nanoparticles have been studied as vessels to carry drugs through the body.
Once they are engineered with antibodies that bind to specific receptors on the
surface of targeted cells, these nanoparticles also can, in principle, become highly
specific to the disease they are designed to treat.
Ruoslahti, a pioneer in the field of cell adhesion—how cells bind to their
surroundings—has developed small chain molecules called peptides that can be
used to target drugs to tumors and atherosclerotic plaques.
“Greater specific attachment exhibited by rod---shaped particles offers several
advantages in the field of drug delivery, particularly in the delivery of drugs
such as chemotherapeutics, which are highly toxic and necessitate the use of
targeted approaches,” the authors wrote in their paper.
The studies demonstrate that nanorods with a high aspect ratio attach more
effectively to targeted cells compared with spherical nanoparticles. The findings
hold promise for the development of novel targeted therapies with fewer
harmful side effects.
We acknowledge support from a California Institute of Regenerative Medicine
Fellowship, a National Science Foundation (NSF) Graduate Research Fellowship
under Grant DGE---1144085, and the Materials Research Science and Engineering
Centers Program of the NSF under Award Division of Materials Research
The study was co---authored by Poornima Kolhar, UC Santa Barbara; Aaron C.
Anselmo, UC Santa Barbara; Vivek Gupta, UC Santa Barbara; Kapil Pant, UC
Santa Barbara; Balabhaskar Prabhakarpandian, UC Santa Barbara; Erkki
Ruoslahti, Sanford---Burnham and UC Santa Barbara; and Samir Mitragotri, UC
About Sanford---Burnham Medical Research Institute
Sanford---Burnham Medical Research Institute is dedicated to discovering the
fundamental molecular causes of disease and devising the innovative therapies
of tomorrow. Sanford---Burnham takes a collaborative approach to medical
research with major programs in cancer, neurodegeneration, diabetes, and
infectious, inflammatory, and childhood diseases. The Institute is recognized for
its National Cancer Institute---designated Cancer Center and expertise in drug
discovery technologies. Sanford---Burnham is a nonprofit, independent institute
that employs 1,200 scientists and staff in San Diego (La Jolla), California, and
Orlando (Lake Nona), Florida. For more information, visit us at
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