Efficient Encapsulation of Plasmid DNA in pH-Sensitive PMPC-PDPA Polymersomes: Study of the Effect of PDPA Block Length on Copolymer-DNA Binding Affinity

We report the self-assembly of a series of amphiphilic diblock copolymers comprising a biocompatible, hydrophilic block, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and a pH-sensitive block, poly(2-(diisopropylamino)ethyl methacrylate) (PDPA), into a dispersion of colloidally stable, nanometer-sized polymersomes at physiological pH and salt concentration. The pH-sensitivity of the PDPA block affords the electrostatic interaction of these block copolymers with nucleic acids at endocytic pH, as a result of the protonation of its tertiary amine groups at pH values below its pK(a). Herein we investigate the effect of PDPA block length on the binding affinity of the block copolymer to plasmid DNA.