Combinatorial siRNA polyplexes for receptor targeting

Abstract

As synthetic small interfering RNA (siRNA) against antitumoral gene targets show promise for cancer treatment, different siRNA delivery systems have sparkled intense investigations. To develop tumor-specific carriers for cytosolic and systemic siRNA delivery, our laboratory has recently generated folate-conjugated targeted combinatorial siRNA polyplexes based on sequence-defined oligomer platform compatible with solid-phase-supported synthesis. These polyplexes presented efficient siRNA-mediated gene silencing in folate receptor-expressing tumors in vitro and in vivo. In this chapter, we provide a brief background on the formulation design and detailed protocols to evaluate polyplex formation, gene silencing efficiency, and receptor-directed cell killing in cancer cells using targeted combinatorial siRNA polyplexes.