pH-responsive zwitterionic copolypeptides as charge conversional shielding system for gene carriers

A novel rapid pH-responssive polymer polyethylenimine-poly(l-lysine)-poly(l-glutamic acid) (PELG) was designed as the shielding system. The zwitterionic copolypeptide PELG with negatively charged at physical pH can act as the shielding system to shield positively charged polyplexes. PELG was used to shield PEI25k/DNA to form ternary polyplex, the polyplex surface zeta potential can change from a negative to positive nearly pH value of 6.9. Because the pH value of tumor extracellular environment is about 6.5, the positive charges on the polyplexes could be restored in tumors, which is beneficial to the electrostatic interactions between positive polyplexes and negative tumor cells, leading to high cell uptake efficiency and high transfection efficiency.