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Research has shown that a particular receptor for the blood protein thrombin is overexpressed by highly metastatic melanoma cells. When activated, this receptor triggers a wide range of biochemical changes that increase the metastatic activity of melanoma cells. To prevent those biochemical changes from occurring, a team of investigators at The University of Texas M.D. Anderson Cancer Center has developed a small interfering RNA (siRNA) agent designed to prevent melanoma cells from making this receptor, which is known as PAR-1, and used a lipid-based nanoparticle to deliver this agent to melanoma cells.
Reporting its findings in the journal Cancer Research, a team of investigators led by Menashe Bar-Eli, Ph.D., Anil Sood, M.D., and Gabriel Lopez-Berestein, M.D., describes its work in designing a neutral liposome nanoparticle to carry its siRNA agent to melanoma cells. Unlike viruses and positively charged liposomes that other investigators have used to deliver siRNA in animal models, the investigators reasoned that neutral liposomes would produce far few adverse reactions while escaping elimination from the body by macrophages.
Using this formulation to treat mice with melanoma, the researchers demonstrated that the nanoparticle was taken up by the tumors and that PAR-1 production dropped dramatically. As a result, twice-weekly injections of this formulation significantly inhibited melanoma growth and dramatically reduced the incidence of metastasis as measured by the number of metastatic lesions in the animals' lungs. The researchers also noted that the PAR-1 siRNA was able to significantly reduce the amount of tumor-triggered angiogenesis in the treated animals.
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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