Glutathione-Responsive Multilayer Coated Gold Nanoparticles for Targeted Gene Delivery

Efficient gene release after intracellular uptake is very important for non-viral gene delivery systems. To construct a glutathione-responsive gene delivery system, we developed gold-cysteamine (AuCM)/plasmid DNA (pDNA)/poly TAT (pTAT)/hyaluronic acid (HA) nanocomplexes (AuCM/pDNA/pTAT/HA) in this study. The AuCM/pDNA/pTAT/HA nanocomplexes possessed a small size less than 200 nm and negative zeta potential of –17 ± 4 mV. The multilayer structure was verified by UV-Vis spectra, surface charges, dynamic light scattering. Morphology was observed by transmission electron microscope. The AuCM/pDNA/pTAT/HA nanocomplexes could completely protect pDNA against enzymatic degradation. These nanocomplexes showed effective cellular uptake in CD44 receptors over-expressed HepG 2 cells in a HA/CD44 interaction dependent manner. Moreover, transfection efficacy was significantly enhanced in AuCM/pDNA/pTAT/HA treated HepG 2 cells compared with AuCM/pDNA/pTAT, and was further enhanced in the presence of GSH, indicating that AuCM/pDNA/pTAT/HA was glutathione-responsive. Biodistribution revealed that AuCM/pDNA/pTAT/HA nanocomplexes mainly accumulated in liver. In conclusion, AuCM/pDNA/pTAT/HA nanocomplexes may serve as glutathione-responsive gene carriers for actively targeting gene delivery to CD44 receptors over-expressed liver cancers.