Folic acid directly modified low molecular weight of polyethyleneimine for targeted pDNA delivery

Abstract

Gene therapy for cancer treatment has been an attractive option in the last 2-3 decades; however, the development of efficient gene delivery systems is still underway. Low molecular weight of polyethyleneimines (LMW PEIs), especially 1.8K PEI, have received much attention due to their low toxicity. Hydrophobic modification is a versatile method to address the poor transfection efficiency of LMW PEIs. In this study, a series of mole ratios of folic acid were grafted to 1.8K PEI for hydrophobic modification and targeting purposes. All PEI-FAX conjugates were characterized by UV absorption, 1H nuclear magnetic resonance spectroscopy (1HNMR), gel electrophoresis, dynamic light scattering (DLS), zeta potential, luminometry, flow cytometry and confocal microscopy. As expected, all PEI-FAX conjugates maintained the low toxicity of 1.8K PEI. With the optimal FA substitution, PEI-FA0.65 conjugate achieved the highest transfection efficiency on several cell lines, nearly 100-fold higher than that of the 1.8K PEI, which could be attributed to the better pDNA binding ability and favourable pH buffering capacity. Furthermore, folate receptor-mediated specific cell uptake of the PEI-FA0.65/pDNA polyplex also played an important role in its high transfection efficiency. With low cytotoxicity and high transfection efficiency, PEI-FA0.65 holds potential for in vivo study.