PEGylated poly(aspartate-g-OEI) copolymers for effective and prolonged gene transfection

Two PEGylated poly(aspartate-g-OEI) cationic copolymers, PEG-b-pAsp-g-OEI (DAO) and OEI-g-pAsp-b-PEG-b-pAsp-g-OEI (TAO), were developed for in vivo gene transfer, and a non-PEGylated copolymer (MAO) was utilized as a control. These copolymers exhibited favorable capacities for condensing plasmid DNA (pDNA) into nanosized particles (90-180 nm) with positive surface charges. Gene transfection efficiency of the copolymers (especially DAO) demonstrated improved performance compared to PEI25k in both HeLa and HEK 293 cell lines in the presence of serum. Although MAO and DAO show similar gene transfection efficiency in vitro, DAO is shown to be more effective in vivo. The potential reason is that PEGylation enhances the serum-resistance of the carriers and prolongs gene transfection in vivo. For TAO, despite its PEG segment, the complex of copolymer-pDNA is encompassed by a cation shell and cannot reduce the serum effects. These results suggest that PEGylated diblock copolymers have potential as non-viral gene carriers in gene delivery systems for in vivo application.