"Intelligent" nanoassembly for gene delivery: in vitro transfection and the possible mechanism.
A new "intelligent" nanoassembly (INA), consisting of a condensed core of pDNA with protamine sulfate (PS) and a dioleoylphosphatidyl ethanolamine (DOPE)-based lipid envelope containing poly(ethylene glycol)-disulfide-DOPE (PSD), was designed and investigated. The in vitro release experiment was carried out in solution containing 10mM of Glutathione, which reflected the redox potential of the intracellular environment. The experimental result indicated that PSD possessed a good ability of self-dePEGylation and could result in efficient release of content in the reductive environment. INAs showed higher transfection efficiency and much lower cytotoxicity compared with Lipofectamine 2000 on HEK 293 cells. Cellular uptake and subcellular localization, as well as the quantitation of nuclear transfer demonstrated that the superior transfection efficiency of INAs could result from both enhanced cellular uptake mediated by DOPE and efficient nuclear delivery mediated by PS. The biodistribution of INAs in nude mice bearing tumor implied that this PSD-based nanoassembly loading PS/DNA could be a promising gene delivery system for tumor therapy.
Xu
Zhenghong
Z
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Chen
Lingli
L
Zhang
Zhiwen
Z
Gu
Wangwen
W
Li
Yaping
Y
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D036103:Nanotechnology / Q000379:methods*; D014162:Transfection / Q000379:methods*