Development of nanocarrier for gene delivery to improve cellular uptake

Abstract

We previously developed modified poly (D, L-lactide-co-glycolide) (PLGA) nanosphere (NS) prepared by an emulsion solvent diffusion (ESD) method as a gene delivery system. In this study, PLGA NS was modified by chitosan (CS) and polysorbate 80 (Tween 80, P80) to improve cellular uptake. We investigated cellular uptake, intracellular distribution and transfection efficiency of P80 modified PLGA NS for a plasmid DNA delivery system in A549 cells. Cellular uptake and transfection efficiency of P80-PLGA NS were greater than CS-PLGA NS. The uptake of unmodifed and CS-PLGA NS was mediated, predominantly, by clathrin-mediated endocytosis. In contrast, specific endocytic pathway could not be determined on cellular uptake of P80-PLGA NS. Intracellular distribution of PLGA NS depended on the surface properties of PLGA NS. P80-PLGA NS did not show cytotoxicity for A549 cells. Thus, P80-PLGA NS could serve as an effective gene delivery system, and the surface properties of PLGA NS are key parameters for optimal intracellular uptake and distribution.