pH-sensitive triblock copolymers for efficient siRNA encapsulation and delivery

A new pH-sensitive triblock copolymer, polyethylene glycol-block-poly(2-dimethylaminoethyl methacrylate)- block-poly(2-diisopropylaminoethyl methacrylate) (PEG-PDMA-PDPA), was synthesized via atom transfer radical polymerization (ATRP). The potential of this polymer for siRNA delivery was assessed. This triblock copolymer formed nanocapsules with high siRNA encapsulation efficiency that protected siRNA from degradation in serum. Capsules were pH-sensitive and deformed when pH decreased below 6. In vitro RNAi evaluation demonstrated that the capsules are capable of delivering siRNA and knocking down GFP expression in HeLa cells in a dose-dependent manner with relatively low cytotoxicity. The novel PEG-PDMA-PDPA triblock copolymer offers insight into the design of pH-sensitive polymers for siRNA delivery.