Degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate and polyethylenimine as a gene carrier: molecular weight of PEI affects transfection efficiency

Abstract

The aim of the research is to study the effect of polyethylenimine (PEI) molecular weight on the gene transfection efficiency of degradable poly(amino ester) based on poly(ethylene glycol) dimethacrylate (PEGDMA) and polyethylenimine (PEG-cr-PEI) as a gene carrier. Various low molecular weight (LMW) branched PEI based PEG-cr-PEI was synthesized via Michael addition. The degradation half-life of PEG-cr-PEI was longer at pH 5.6 than that at pH 7.4. The plasmid condensation and protection ability of the PEG-cr-PEI were confirmed by agarose gel electrophoresis assay. PEG-cr-PEI/DNA nanoparticles showed high positive zeta potential (>+20 mV), narrow size distribution, and spherical shapes with size below 250 nm when N/P ratios of PEG-cr-PEI to DNA were above 10, suggesting that they have endocytosis potential. The cytotoxicity of PEG-cr-PEI/DNA complexes was lower than that of PEI 25K/DNA complexes, and the transfections mediated by PEG-cr-PEI were checked in 293T, HeLa and HepG2 cell lines. The report gene expression was increased with increasing the molecular weight of LMW PEI. The "proton sponge effect" was proposed as the mechanism of PEG-cr-PEI mediated gene transfection.