Effect of PEI surface modification with PEG on cytotoxicity and transfection efficiency

Polyethylenimine (PEI) is a cationic polymer with high transfection efficiency as non-viral gene delivery agent that exhibits promising features for gene therapy applications due to its cationic charge and thus favourable DNA-condensing abilities; however, its high cytotoxicity restricts its application. The cellular toxicity of PEI molecules depends on their structure, molecular weight and surface charge density. To improve the properties of branched 25 kDa PEI as a non-viral gene delivery agent, this polymer was conjugated to polyethylene glycol (PEG) molecules at three different molar ratios of 10, 20 and 30. The degree of PEG grafting was determined by 2, 4, 6-trinitrobenzene sulphonic acid assay. The effects of various PEGylation degrees on cellular toxicity and transfection ability of PEI polymer were assessed on BT-474 and MCF-10A cell lines. Compared to unmodified PEI, PEG-grafted PEI copolymers demonstrated reduced cytotoxicity, particularly at higher PEG grafting ratios. Among different PEG-grafted PEIs, the PEG-PEI copolymer which grafted to PEG at a molar ratio of 10:1 had the highest transfection efficiency in both cell lines. The findings of this Letter showed that these PEG-grafted PEI copolymers have desirable gene transfection efficiency and favourable biocompatibility for gene delivery.