Bioreducible poly(amidoamine)s with charge-reversel properties for intracellular protein delivery

An effective intracellular protein delivery system was developed using bioreducible disulfide-containing poly(amidoamine)s with negatively charged citraconic side groups that can give charge-reversal upon pH decrease. These water-soluble and linear polymers efficiently self-assemble with proteins into nanocomplexes by charge attraction. Intracellular-mimicking protein release from the particles is triggered by the reduction of polymer disulfide linkages, causing polymer degradation, and inversion of protein-polymer interaction at endosomal pH due to the charge-reversal of the citraconic side group