Recent advances in the design, development, and targeting mechanisms of polymeric micelles for delivery of siRNA in cancer therapy

Small interfering RNA (siRNA) is a relatively novel nucleic acid-based therapy to treat diseases such as cancer. Nevertheless, substantial obstacles to its clinical applications have been reported, such as low cellular uptake, immunogenicity, off-target effects, and instability in physiological environments. The design of appropriate delivery vehicles capable of transporting siRNA to target cells has been pursued. Nanoparticies are extensively studied for the delivery of siRNA. Among the various nanocarriers, polymeric micelles have recently gained strong interest. Polymeric micelles of average nanometer size are straightforward to design and modify. Hydrophilic groups incorporated in the polymeric micelles can extend in vivo half-life of siRNA to ensure adequate accumulation in tumors, be exchanged for cations that electrostatically interact with siRNA, and be coupled to various ligands for cell-specific targeting. The polymeric micelle core provides stability and serves as a loading dock for drugs. In this review, the different types of polymers used, the design and characterization of polymeric micelles for siRNA delivery, and the established polymeric micelle targeting mechanisms are discussed. (C) 2016 Elsevier Ltd. All rights reserved.