Development of Functional Materials for Sirna Delivery and Neural Tissue Engineering

Abstract

The current nonviral siRNA delivery systems in the literature face many problems such as, cellular entry, endosomal escape and efficient siRNA release. Considering this motive, we developed gold nanoparticles (AuNPs) and temperature/pH responsive pentablock copolymer based siRNA delivery systems to address these problems. The temperature and pH responsive cationic and amphiphilic pentablock copolymers, which were consisted of the temperature responsive Pluronic F127 middle block constructed by PEO-PPO-PEO ((poly(ethyleneoxide)-block-poly(propyleneoxide)-block-poly(ethyleneoxide))) blocks contributing cellular entry through temperature responsive micellization and pH responsive cationic PDEAEM (poly(2-diethylaminoethyl methacrylate)) end blocks facilitating nucleic acid condensation and endosomal escape, were used for the first time in the development of polyplex and AuNP based multicomponent siRNA delivery systems (MCSs). The results indicated that systems managed to protect siRNA from external effects, maintain the system stability, facilitate cellular entry and enhance endosomal escape. It was noted that the transfection efficiency of the MCSs, which were boosted by the presence of cleavable disulfide bond, was ~15% higher than the commercial product RNAiMax while the efficacy of polyplexes alone were similar to the RNAiMax.