title: Synthesis and gene transfection activity of cyclen-based cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails.
abstract: A series of novel 1,4,7,10-tetraazacyclododecane (cyclen)-based cationic lipids with asymmetric double hydrophobic tails (cholesteryl and long aliphatic chains) were designed and synthesized. Lysine was chosen as a linking moiety in the molecular backbone. The liposomes formed from 8 and dioleoylphosphatidylethanolamine (DOPE) could bind and condense plasmid DNA into nanoparticles under a low N/P ratio. These nano-scaled lipoplexes have low cytotoxicity, and might efficiently transfect A549 cells. In vitro transfection results revealed that all cationic lipids showed a comparable or better transfection efficiency (TE) than commercially available Lipofectamine 2000. The length and saturation degree of the aliphatic chain would affect their gene transfection performance, and the linoleic acid-containing 8e could give the best TE.
authors.affiliation: Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu, 610064, China. jzhang@scu.edu.cn xqyu@scu.edu.cn.
authors.forename: Bao-Quan
authors.initials: BQ
authors.lastname: Liu
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yi
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Fan
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D000215:Acylation / Q000187:drug effects; D002412:Cations; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry*; D000080027:Cyclams; D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D024202:Electrophoretic Mobility Shift Assay; D004996:Ethidium / Q000378:metabolism; D005453:Fluorescence; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D055672:Static Electricity; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; C038072:cyclen; D002784:Cholesterol; D004996:Ethidium