Development of an siRNA delivery system using a cancer-specific cell-penetrating peptide

Abstract

RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment. Additionally, the BR2-VEGF siRNA complex exhibited significant serum stabil-ity and high levels of gene-silencing effects in vitro. Moreover, the transfection efficiency of the complex into a cancer cell line was higher than that observed in non-cancer cell lines, resulting in downregulated in-tracellular VEGF levels in HeLa cells and comprehensively improved antitumor efficacy in the absence of significant toxicity. These results indicated that BR2 has significant potential for safe, efficient, and specific delivery of siRNA for diverse applications.