The strategy to improve gene transfection efficiency and biocompatibility of hyperbranched PAMAM with the cooperation of PEGylated hyperbranched PAMAM

Abstract

As a promising non-viral gene vector, cationic polyamidoamine (PAMAM) dendrimer could form complexes with negative charged DNA to mediate efficient gene delivery in vitro and in vivo. However, complicated synthesis technology and potential cytotoxicity limited their application in clinical translational researches. Hyperbranched polyamidoamine (h-PAMAM), which could be synthesized by a simpler one-pot method, has similar properties with PAMAM, and PEGylation modification of h-PAMAM has been used to reduce cytotoxicity. Here we prepared gene delivery system with h-PAMAM and h-PAMAM derivative h-PAMAM-g-PEG, respectively and found that the viability of cells with h-PAMAM-g-PEG was quite higher in comparison with cells with unmodified h-PAMAM. However, gene delivery efficiency was lower with h-PAMAM-g-PEG. Then we used mixture composed of h-PAMAM and h-PAMAM-g-PEG and such composition was designed to reduce cytotoxicity while maintaining high transfection efficiency. Our results indicated that this mixture system of h-PAMAM and h-PAMAM-g-PEG achieved higher transfection efficiency and lower cytotoxicity compared with h-PAMAM-only system.