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.
Feifei
F
Yu
Jingbin
J
Huang
Yuan
Y
Yu
Ying
Y
Lu
Yan
Y
Chen
He
H
Zhang
Guichen
G
Zhou
Zhiguo
Z
Sun
Junjie
J
Liu
Duxin
D
Sun
Guoqing
G
Zhang
Hao
H
Zou
Yanqiang
Y
Zhong
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D018390:Gene Targeting / Q000379:methods*; D005978:Glutathione / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D014162:Transfection / Q000379:methods*
D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D006046:Gold; D004247:DNA; D005978:Glutathione