Nov 20 2008
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.
This work, which was funded by the NCI, is detailed in the paper “Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA.” An abstract of this paper is available at the journal’s Web site.
View abstract