title: Novel cholesterol-based cationic lipids as transfecting agents of DNA for efficient gene delivery.
abstract: The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-L-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/-) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yqyhjj@fmmu.edu.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. hmlkuohu@fmmu.edu.cn.
authors.forename: Meng-Lei
authors.initials: ML
authors.lastname: Huan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yaoji1316@fmmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Wan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yaojishi@fmmu.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. zhousy@fmmu.edu.cn.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. blezhang@fmmu.edu.cn.
authors.forename: Bang-Le
authors.initials: BL
authors.lastname: Zhang
mesh_terms: D002412:Cations / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D008081:Liposomes / Q000737:chemistry / Q000633:toxicity; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D014162:Transfection
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D002784:Cholesterol