Natural polyphenol inspired polycatechols for efficient sirna delivery

There is a continuing quest to rationally fabricate polymeric biomaterials with both high transfection efficiency and minimal toxicity for the emerging opportunities in small interfering RNA (siRNA) delivery. Recently, this goal was promoted highly by developing a robust and efficient strategy to facilitate polymer-mediated RNAi using natural polyphenols with multiple phenol groups that could condense siRNA effectively into negatively charged nanoparticles (NPs). Further coating of these NPs with cationic polymers of low molecular weight enabled their intracellular siRNA delivery. Inspired by the structural and functional features of natural polyphenols, we aimed to further the development of low molecular weight polycatechols as a new class of efficient and biocompatible polymers for siRNA delivery in our current study. The fabricated polycatechols have benefits of requiring only one-step fabrication toward efficient siRNA nanoformulations. Moreover, they could deliver siRNA into cells and silence target genes both in vitro and in vivo. The resulting polycatechol/siRNA formulations were also functionally competent, demonstrating a successful, profound downregulation of a proinflammatory enzyme to attenuate chronic intestinal inflammation in an intestinal injury model. This study provides a new approach in chemistry for the development of efficient synthetic polymers for therapeutic siRNA delivery.