A Highly Entangled Polymeric Nanoconstruct Assembled by siRNA and its Reduction-Triggered siRNA Release for Gene Silencing

Abstract

A nanoconstruct (NC) is developed from a biocompatible natural polymer and siRNA conjugates to deliver small interfering RNA (siRNA) target-specifically without cationic condensation reagents. This study reports a novel siRNA-mediated cross-linked NC produced by hybridizing two complementary single-stranded siRNAs that are conjugated to the polymer dextran via a disulfide linkage. The reducible disulfide bond between the siRNA and polymer allow siRNA release from the NC in the reducible cytoplasmic region after the NC enters the cell. In addition, when the NC contains the prostate-carcinoma-binding peptide aptamer DUP-1, it can selectively deliver siRNA into prostate cancer cells of the PC-3 lines; thus, the newly formulated NC has reduced the cytotoxicity and improved the efficacy of target-specific siRNA delivery. Moreover, this new concept of NCs using biocompatible siRNA and a neutral polymer may provide insightful knowledge for future directions for designing NCs for stimuli-responsive and advanced target-specific siRNA delivery.