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Improving Drug Delivery

Chemotherapy: Light activation improves penetration and efficacy of nanoparticles as carriers

by Puneet Kollipara
November 11, 2013 | A version of this story appeared in Volume 91, Issue 45

A schematic showing how chemotherapy-carrying nanoparticles (left) penetrate deeper into tumor sites and decompress blood vessels after the tumors are irradiated with ultraviolet light (right).
Credit: Modified from Proc. Natl. Acad. Sci. USA
Nanoparticles carrying a cancer drug are administered to mice and exposed to UV light, causing them to contract and release the drug into tumors.

Nanoparticles are promising cargo ships for targeted drug delivery. But the materials have had limited success treating cancer, because they often can’t penetrate deep into tumors. The nanoparticles are stalled by the extracelluar matrix and compressed blood vessels.

Scientists have shone new light on the problem—literally—by deploying drug-carrying polymer nanoparticles that contract and gradually squeeze out their cargo when exposed to ultraviolet light. When mice with tumors are injected with the nanoparticles, shining light through the skin at the tumor sites boosts drug release, killing cancer cells (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1315336110).

The research, by Daniel S. Kohane of Boston Children’s Hospital, Rong Tong of Massachusetts Institute of Technology, and coworkers, builds on their work designing nanoparticles that reversibly contract and expand when exposed to light of certain wavelengths. The researchers implanted mice with fibroblastic sarcomas, just under the skin. They first injected nanoparticles containing a fluorescent dye into tumors as a tracer. Some tumors were irradiated with UV light, and others were not. The irradiated tumors showed a greater spread of the nanoparticles.

Scientists then injected nanoparticles containing the cancer drug docetaxel into mice intravenously. Circulating blood carried most of the particles through the UV light on the tumor, activating them. Mice treated in this way had half as many cancer cells as control mice and larger diameter blood vessels in the tumor.

The researchers caution that UV light can’t penetrate far into the body, so light endoscopy or near-infrared-triggered nanoparticles might be necessary to reach deep tumors. The work was partially funded by the French pharmaceutical firm Sanofi.

The current method’s limitations aren’t trivial, says biomedical engineer Jonathan F. Lovell of the University at Buffalo, SUNY, but such light-driven techniques could “address significant unmet medical needs in the clinic one day.”



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