DC-Chol/DOPE cationic liposomes: A comparative study of the influence factors on plasmid pDNA and siRNA gene delivery

被引:135
作者
Zhang, Yang [1 ,2 ]
Li, Huimei [1 ,2 ,3 ,4 ,5 ]
Sun, Jing [1 ,2 ]
Gao, Jie [1 ,2 ,3 ,4 ,5 ]
Liu, Wei [1 ,2 ]
Li, Bohua [1 ,2 ,3 ,4 ,5 ]
Guo, Yajun [1 ,2 ,3 ,4 ,5 ]
Chen, Jianming [1 ,2 ]
机构
[1] Second Mil Med Univ, Sch Pharm, Dept Pharmaceut Sci, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Int Joint Canc Inst, Shanghai 200433, Peoples R China
[3] PLA Postgrad Sch, Gen Hosp Canc Ctr 301, Beijing 100853, Peoples R China
[4] Natl Engn Res Ctr Antibody Med, Shanghai, Peoples R China
[5] Shanghai Key Lab Cell Engn & Antibody, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
DC-Chol; DOPE; Cationic liposomes; pDNA; siRNA; Transfection; IN-VITRO; PHYSICOCHEMICAL CHARACTERIZATION; TRANSFECTION EFFICIENCY; REDUCED TOXICITY; COMPLEXES; VECTORS; THERAPY; LIPIDS; SERUM; VIVO;
D O I
10.1016/j.ijpharm.2010.01.035
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cationic liposomes (CLs) composed of 3 beta(N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) (DC-Chol/DOPE liposomes) have been classified as one of the most efficient gene delivery systems. Our study aims to examine the effect of the molar ratio of DC-Chol/DOPE, PEGylation and serum on the pDNA (plasmid pDNA) and siRNA (small interfering RNA) transfection of DC-Chol/DOPE liposomes. The results showed that the most efficient DC-Chol/DOPE liposomes for pDNA or siRNA delivery were at a 1:2 or 1:1 molar ratio of DC-Chol/DOPE, respectively. The transfection efficiency of DC-Chol/DOPE liposomes increased along with increased weight ratio of DC-Chol/siRNA. However, the pDNA transfection efficiency decreased along with increased weight ratio of DC-Chol/pDNA from 3/1. As expected, PEGylation decreased siRNA and pDNA transfection efficiency of DC-Chol/DOPE liposomes. In PEGylated DC-Chol/DOPE liposomes, increased weight ratio of DC-Chol/pDNA from 3/1 did not lead to higher pDNA transfection efficiency, whereas increased weight ratio of DC-Chol/siRNA resulted in increased siRNA transfection efficiency. Furthermore, the serum did not significantly inhibit the pDNA and siRNA transfection efficiency of DC-Chol/DOPE liposomes. In conclusion, our results elucidated the influence factors of DC-Chol/DOPE liposome transfection and would reveal that siRNA and pDNA transfection mechanisms were different in DC-Chol/DOPE liposomes. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:198 / 207
页数:10
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