siRNA delivery systems for cancer treatment

With increasing knowledge on the molecular mechanisms of endogenous RNA interference, small interfering RNAs (siRNAs) have been emerging as innovative nucleic acid medicines for treatment of incurable diseases such as cancers. Although several siRNA candidates for the treatment of ocular and respiratory diseases are undergoing clinical trials, there are challenges inherent in the further development of siRNAs for anti-cancer therapeutics, because systemic administration will be required in most cases. In addition to nonspecific off-target and immune stimulation problems, appropriate delivery remains a major hurdle. The technologies developed for delivery of nucleic acid medicines such as plasmid DNA and antisense oligonucleotides have paved the way to rapid progress for in vivo delivery of siRNAs. Here, we review various in vivo delivery strategies including chemical modification, conjugation, lipid-based techniques, polymer-based nanosystems, and physical methods. Moreover, the current progress in siRNA delivery systems for gynecologic, liver, lung, and prostate cancers is discussed. (C) 2009 Elsevier B.V. All rights reserved.