Cancer therapy with novel siRNA delivery bioreducible polymer

Abstract

Arginine-grafted Bioreducible Polymer (ABP) could deliver significant amounts of DNA and siRNA into the cytoplasm. We made a melanoma cancer model by subcutaneously injecting murine melanoma cells (B16F10 cells) into C57BL/6 mice and then tested that ABP/siRNA effected on the various cell lines in vitro or in vivo systems. The B16F10 mouse model of melanoma shows that tumor angiogenesis is a critical process involved in solid tumor growth. Within 3~5days after tumor challenge, B16-F10 rapidly develops a network of tumor vasculature and up-regulates expression of the proangiogenic vascular endothelial growth factors. Upregulation of proangiogenic factors and downregulation of antiangiogenic factors define a molecular signature in growing tumors, called the angiogenic switch. Taking advantages of ABP holding genes, leading higher transfection effeciency and having lower cytotoxicity and designing a combinational siRNA silencing the genes related to antiapoptosis may become a potent candidate drug for cancer therapy. Here, we confirmed the possibilities of siRNA and ABP polyplex as antitumoral drugs through accomplishing melanoma studies basically using various siRNA silencing endogenous mRNA.