RNAi therapeutics: Current status of nanoncologic siRNA delivery systems

With the growing comprehensive understanding of antisense gene silencing and the mechanism of RNA interference (RNAi), small interfering RNA (siRNA) has gained tremendous attention as a putative therapeutic agent for cancer therapy and other diseases. Due to its inherent target specificity, siRNA has the potential to inhibit tumor cell proliferation, metastasis and retard tumor growth, all-the-while avoiding off-target and adverse effects that are commonly observed with conventional anti-cancer drugs. There are a few ongoing clinical trials using siRNA for cancer treatment and other diseases. However, to date, none have been approved by FDA. Crucial for clinical success, delivery reagents that promote cellular uptake of the siRNA, maintain its stability in the presence of nucleases and prevent potential immunogenicity in vivo are required. Therefore, in recent years, a wide range of siRNA delivery systems have been developed and evaluated. In this review, we describe the major strategies currently employed for siRNA delivery followed by a presentation of the most recent works using such a variety of delivery systems and carriers in different cancers.