Targeting highly metastatic melanomas with nanotechnology

Specially designed small RNA molecules have proven very effective in decreasing the expression of specific genes that cancer cells need to survive; however, getting these RNA molecules inside cancer cells in living animals is difficult. Using a promising nanotech approach to deliver the RNA molecules, a type of nanoparticle described as a neutral liposome was administered to mice bearing melanoma tumors and found to cause a significant decrease in tumor growth and in the number of metastatic tumor colonies. From the National Cancer Institute’s Alliance for Nanotechnology in Cancer “Nanoparticle Targets Melanoma With siRNA“:

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 [abstract], 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.


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