A smart nanoassembly consisting of acid-labile vinyl ether PEG-DOPE and protamine for gene delivery: preparation and in vitro transfection.
The conception of a modular designed and viruslike nonviral vector has been presented for gene delivery. Recently, we constructed a new smart nanoassembly (SNA) with multifunctional components that was composed of a condensed core of pDNA with protamine sulfate (PS) and a dioleoyl phosphatidylethanolamine (DOPE)-based lipid envelope containing poly(ethylene glycol)--vinyl ether--DOPE (PVD). SNAs with mPEG 2000 (SNAs1) or mPEG 5000 (SNAs2) loading PS/DNA were prepared by the lipid film hydration technique. The particle size was about 160 nm for SNAs1 and 240 nm for SNAs2 loading PS/DNA (10:1 w/w), and the zeta potential was about 4 mV for two SNAs. The in vitro release experiment indicated that PVD possessed a good ability for self-dePEGylation, which could result in the recovery of an excellent fusogenic capacity of DOPE at low pH. SNAs showed a higher transfection efficiency and much lower cytotoxicity than did Lipofectamine 2000 on HEK 293, HeLa, and COS-7 cells. The cellular uptake and subcellular localization demonstrated that the superior transfection efficiency of SNAs could result from the fact that the DOPE-based lipid envelope containing PVD increased PS/DNA in the cytoplasm, and protamine enhanced the nuclear delivery or overcame the nuclear membrane barrier. These results implied that the PVD-based nanoassembly loading PS/DNA could be a promising gene delivery system.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhenghong
Z
Xu
Wangwen
W
Gu
Lingli
L
Chen
Yu
Y
Gao
Zhiwen
Z
Zhang
Yaping
Y
Li
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000493:pharmacokinetics*; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures / Q000737:chemistry*; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D011479:Protamines; D014162:Transfection / Q000379:methods*; D014753:Vinyl Compounds
D010714:Phosphatidylethanolamines; D011479:Protamines; D014753:Vinyl Compounds; C094877:dioleoyl phosphatidylethanolamine; C100195:vinyl ether; D011092:Polyethylene Glycols; D004247:DNA