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A multifunctional drug delivery system consisting of a lipid-based nanoparticle, a standard anticancer drug, and a short nucleic acid designed to augment the activity of that drug has demonstrated the ability to treat drug-resistant tumor cells. This work, published in the journal Clinical Cancer Research, suggests a novel approach to treating drug-resistant tumors, the leading cause of cancer deaths.
Tamara Minko, Ph.D., of Rutgers University, led the team of investigators that developed this novel nanotherapeutic system for treating cancer. She and her colleagues set out to target a signaling pathway that causes tumors to trigger new blood vessel growth and to develop resistance to many anticancer drugs. To shut down this pathway, the investigators developed an antisense oligonucleotide that would bind to and inactivate messenger RNA coding for a protein known as hypoxia-inducible factor-1α, which, when present, activates the targeted pathway.
To deliver this antisense agent to tumor cells, the investigators created a lipid-based nanoparticle, or liposome, that would stably incorporate both the antisense agent and the anticancer drug doxorubicin. The investigators also created two additional liposomes as controls, each of which was loaded with only one of the two therapeutic agents. Tests with both isolated tumor cells and with animals bearing human tumors showed that administration of the multifunctional nanoparticle was more effective at killing tumor cells than was coadministration of the two single-component liposomes. At the same time, the multifunctional liposome produced fewer side effects than did the combination of the two single-component liposomes. The investigators hypothesized that cells may have a limited ability to take up liposomes, so including both drugs in a single liposome would increase cellular uptake of the active ingredients relative to when these agents are delivered using two separate liposomes.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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