A novel polymer-lipid hybrid nanoparticle for efficient nonviral gene delivery

Aim： To develop a novel non-viral vector with high transfection efficiency and low cytotoxicity. Methods： Poly （ethylene glycol）-distearoylphosphatidylethanolamine （PEG-DSPE） was incorporated into polymer-lipid hybrid nanoparticles （PLN） to construct a PEG-DSPE modified long circulating PLN （L-PLN）. The L-PLN was prepared by the emulsifying-solvent evaporation method, L-PLN and L-PLN/DNA complexes were characterized. Both HEK293 and MDA-MB-231 cells transfected by L-PLN/DNA complexes were observed under a fluorescence microscope. The transfection efficiency of the complexes to HEK293 cells was further evaluated by flow cytometry. Results： The GFP fluorescence intensity in HEK293 cells transfected by the L-PLN/DNA complexes （N/P=10） was about 37.2%, which was higher than those transfected by PLN alone or commercial LipofectamineTM 2000. The L-PLN exhibited minimal toxicity at a low N/P ratio compared with other vectors. Conclusion： L-PLN as a novel gene delivery system, has higher transfection efficiency and acceptable cytotoxicity compared to the corresponding PLN, which is beneficial for the development of non-viral gene transfer vectors and may offer an alternative strategy for the future gene therapy.