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Responsive pentablock copolymers for siRNA delivery
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In this study, temperature and pH responsive cationic and amphiphilic pentablock copolymers, which consist of the temperature responsive triblock Pluronic F127 sandwiched between pH responsive PDEAEM (poly(2-diethylaminoethyl methacrylate)) end blocks, were used for the first time in the development of polyplex and gold nanoparticle (AuNP) based multicomponent siRNA delivery systems (MCSs). Copolymers in both systems protected siRNA from external effects, provided cell entry and endosomal escape. The thermoreversible micellization of the hydrophobic PPO block facilitated the cellular entry while the PDEAEM blocks enhanced the endosomal escape through protonated tertiary amine groups by pH buffering. The synergistic advantages of the different blocks showed an enhanced effect in the MCSs due to attachment and surface configuration reasons. The siRNA transfection efficiency of MCSs against luciferase expressing SKOV3 cells was 15% higher than both the polyplexes alone and the commercial siRNA transfection agent Lipofectamine RNAiMax at the same applied dose, without any toxicity. The results indicated that the multicomponent systems based on the responsive cationic pentablock copolymers and gold nanoparticles have promising potential as an efficient siRNA delivery vector for future applications.