pH-Responsive PEGylated Gene Delivery System

The pH-sensitive polyethylene glycol-grafted polyethylenimine (mPEG-CH=N-PEI) was synthesized via benzoic imine linker according to the acidic environment of endosomal. The corresponding stable PEGylated polyethylenimine (mPEG-PEI) without pH-sensitivity was synthesized as control. The results showed that both PEGylated polycations could condense DNA into tight spherical nanoparticles about 80 nm in size and 10 mV in-potential, which showed excellent stability under physiological conditions. The benzoic imine linkers were easily cleaved under the pH of 5, which was similar with the endosomal pH. Human hepatoblastoma cell line (HepG2) cell culture results indicated that the cytotoxicity and cellular uptake efficiency of both PEGylated gene nanoparticles decreased remarkably because of the shielding effect of PEG shell. Due to the cleavage of benzoic imine linker at acidic environment of endosomal, the PEG shell of mPEG-CH=N-PEI/DNA polyplexes was detachable and lead to quick endosomal escape. So mPEG-CH=N-PEI/DNA polyplexes showed higher gene expression than the mPEG-PEI/DNA polyplexes. Based on these results, we concluded that PEGylated polyplexes via benzoic imine linkers showed high extracellular stability, intracellular DNA release and effective gene transfection.