title: Novel gemini cationic lipids with carbamate groups for gene delivery.
abstract: To obtain efficient non-viral vectors, a series of Gemini cationic lipids with carbamate linkers between headgroups and hydrophobic tails were synthesized. They have the hydrocarbon chains of 12, 14, 16 and 18 carbon atoms as tails, designated as G12, G14, G16 and G18, respectively. These Gemini cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. The DNA-bonding ability of these Gemini cationic liposomes was much better than their mono-head counterparts (designated as M12, M14, M16 and M18, respectively). In the same series of liposomes, bonding ability declined with an increase in tail length. They were tested for their gene-transferring capabilities in Hep-2 and A549 cells. They showed higher transfection efficiency than their mono-head counterparts and were comparable or superior in transfection efficiency and cytotoxicity to the commercial liposomes, DOTAP and Lipofectamine 2000. Our results convincingly demonstrate that the gene-transferring capabilities of these cationic lipids depended on hydrocarbon chain length. Gene transfection efficiency was maximal at a chain length of 14, as G14 can silence about 80 % of luciferase in A549 cells. Cell uptake results indicate that Gemini lipid delivery systems could be internalised by cells very efficiently. Thus, the Gemini cationic lipids could be used as synthetic non-viral gene delivery carriers for further study.
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116021, Liaoning, China ; SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China.
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Zhao
authors.affiliation: Pharmaceutical and Analytical R&D, Roche, New Jersey 07110, USA.
authors.forename: Farooq
authors.initials: F
authors.lastname: Qureshi
authors.affiliation: SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China.
authors.forename: Shu-Biao
authors.initials: SB
authors.lastname: Zhang
authors.affiliation: SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China.
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cui
authors.affiliation: SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China.
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116012, Liaoning, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116021, Liaoning, China.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Zhang
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang