Targeted delivery of RNAi therapeutics for cancer therapy.

Since the discovery of RNA interference (RNAi) [1], siRNA) has become the focus of attention for pharmaceutical development. siRNA is more potent than antisense oligo­ nucleotides owing to the endogenous mecha­ nism of action catalyzed by the RNA­induced silencing complex [2]. Many oncogenic targets involved in survival, specifically antiapoptosis, angiogenesis and drug resistance, have been tested for siRNA­mediated cancer therapy. However, siRNA can only become an anti cancer agent when it is specifically and effectively deliv­ ered to the target cells in vivo [3]. An ideal siRNA delivery vehicle for cancer therapy must be able to evade the reticuloendothelial system to be effectively taken up by the tumor cells and to escape from the endosome after endocytosis. The existence of a leaky vasculature in most of the solid tumors supports the enhanced per­ meability and retention effect for nanoparticle (NP)­mediated delivery of anticancer agents, for example the successful Doxil formulation of doxorubicin. A well­designed NP of less than 200 nm in diameter is suitable for siRNA delivery to the tumor. NPs composed of differ­ ent materials have been developed for siRNA delivery. Two major classes of biomaterials have been employed for siRNA delivery. They will be discussed separately in this article.