Development of a Novel Low Toxicity and High Efficiency PEI-Based Nanopolymer for Gene Delivery In Vitro and In Vivo

Abstract

Polyethylenimine/(PEI) is one of the most popular cationic polymers for non-viral gene delivery. Although high molecular weight PEI has relatively high effi ciency, its associated high cytotoxicity limits its use as a successful gene delivery agent. Here, we developed a novel polymers named as H1, which consisted of low molecular weight PEI (600 Da), cyclodextrin and folate, we demonstrated that H1 condensed plasmid DNA to a compact globe-like polyplexes with about 100nm in diameter. The polyplexes showed higher transfection effi ciency and lower cytotoxicity in various tumor cell lines in vitro, compared with high molecular weight PEI/(25Kd). Importantly, the effi ciency of H1-mediated transfection comparable to that of Adenovirus at the early stage of post intratumoral injection in living mice as shown by in vivo imaging and no toxicity response was detected by histochemical staining of the tumor tissue. In addition, H1-mediated pEGFP showed high transfection effi ciency in C2C12 (mouse myoblast cells) in vitro and intramuscular injection of H1/ pLuc revealed robust bioluminescence signal in the thigh muscle of living mice. These results clearly show that H1 is a safe and effective polyplex forming agent for plasmid transfections.