title: Synthesis and optimization of cholesterol-based diquaternary ammonium Gemini Surfactant (Chol-GS) as a new gene delivery vector.
abstract: Amongst a number of potential nonviral vectors, cationic liposomes have been actively researched, with both gemini surfactants and bola amphiphiles reported as being in possession of good structures in terms of cell viability and in vitro transfection. In this study, a cholesterol-based diquaternary ammonium gemini surfactant (Chol-GS) was synthesized and assessed as a novel nonviral gene vector. Chol-GS was synthesized from cholesterol by way of four reaction steps. The optimal efficiency was found to be at a weight ratio of 1:4 of lipid:DOPE (1,2-dioleoyl-L-alpha- glycero-3-phosphatidylethanolamine), and at a ratio of between 10:1~15:1 of liposome:DNA. The transfection efficiency was compared with commercial liposomes and with Lipofectamine, 1,2-dimyristyloxypropyl-3-dimethylhydroxyethylammonium bromide (DMRIE-C), and N-[1-(2,3-dioleoyloxy)propyl]- N,N,N-trimethylammonium chloride (DOTAP). The results indicate that the efficiency of Chol-GS is greater than that of all the tested commercial liposomes in COS7 and Huh7 cells, and higher than DOTAP and Lipofectamine in A549 cells. Confirmation of these findings was observed through the use of green fluorescent protein expression. Chol-GS exhibited a moderate level of cytotoxicity, at optimum concentrations for efficient transfection, indicating cell viability. Hence, the newly synthesized Chol-GS liposome has the potential of being an excellent nonviral vector for gene delivery.
authors.affiliation: School of Life Sciences and Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu, 702-701, Korea.
authors.forename: Bieong-Kil
authors.initials: BK
authors.lastname: Kim
authors.forename: Kyung-Oh
authors.initials: KO
authors.lastname: Doh
authors.forename: Yun-Ui
authors.initials: YU
authors.lastname: Bae
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Seu
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000737:chemistry*; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis*; D013501:Surface-Active Agents / Q000138:chemical synthesis*
chemical_list: D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; D002784:Cholesterol