RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicines with their preclinical applications and efficacy. Future perspectives in cancer treatment are discussed including promising concomitant treatment with chemotherapies or other siRNA. The outcomes in human clinical trials are also presented.

Several siRNA (small interfering RNA) therapeutics are undergoing clinical trials for cancer, respiratory diseases or macular degeneration, but most are administrated locally. In order to overcome the different barriers to attain an efficient siRNA action after systemic administration, nanocarriers able to carry and protect siRNA are awaited. With this aim, we developed a new platform of siRNA lipid nanocapsules (LNCs) using different cationic lipids, combining the properties of LNCs (siRNA protection and targeting) and lipoplexes (efficient siRNA delivery into the cell). The formulation was revealed to contain different compartments. A siRNA quantification method based on UV spectroscopy was developed to locate and quantify siRNA in each compartment. All in all, these novel siRNA LNCs presented sizes of about 55 nm with a neutral surface charge and siRNA encapsulation efficiencies up to 65% representing appropriate characteristics for systemic administration.