Regulated protonation of polyaspartamide derivatives bearing repeated aminoethylene side chains for efficient intracellular siRNA delivery with minimal cytotoxicity.

The effects of the repeated number (RN) of aminoethylene (AE) units in polyaspartamide side chains were investigated for polyion complex (PIC)-based siRNA delivery. Reduction of the apparent RN from 3 to 2 by thiourea introduction increased a protonatable amine fraction in AE units at endosomal pH, leading to the efficient endosomal escape of siRNA-loaded PICs.