Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (04): 585-592.DOI: 10.6023/A12121016 Previous Articles     Next Articles



付云, 王海蛟, 张骥, 余孝其   

  1. 四川大学化学学院 绿色化学与技术教育部重点实验室 成都 610064
  • 投稿日期:2012-12-08 发布日期:2013-02-06
  • 通讯作者: 余孝其
  • 基金资助:

    项目受973计划(Nos. 2012CB720603, 2013CB328900)和国家自然科学基金(No. 21232005)资助.

Design, Synthesis and Gene Transfection Activity of Macrocyclic Polyamine-Imidazolium Based Cationic Lipids

Fu Yun, Wang Haijiao, Zhang Ji, Yu Xiaoqi   

  1. Key Laboratory of Green Chemistry and Technology-Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China
  • Received:2012-12-08 Published:2013-02-06
  • Supported by:

    Project supported by the National Program on Key Basic Research Project of China (973 Program, 2012CB720603, 2013CB328900) and the National Natural Science Foundation of China (No. 21232005).

A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In this study, four cyclen-based amphiphilic molecules including lauric acid moieties were designed and synthesized, and their molecular structures were confirmed by NMR and ESI-MS. These molecules have a hydrophilic cyclen headgroup and a hydrophobic long chain linking by alkyl or glycol chain, leading to different hydropohobic properties. Cationic liposomes were prepared by mixing the molecules with DOPE at various mole ratios. Agarose gel electrophoresis demonstrated that the liposomes 8a could condense plasmid DNA at N /P molar ratio of 4, and the ratios was 6 for 8b8d. Fluorescence quenching assay also suggested that lipids 8 have good DNA binding ability. The sizes of the formed lipoplexes were measured to be around 80~120 nm, while zeta-potentials of the liposomes were found to be +25~55 mV, and both of these values could remain with little change within 7 d. Among the four lipids, 8a showed moderate in vitro gene transfection efficiency toward A549 cells, and the best transfection could be observed at N/P of 4 with 8a/DOPE ratio of 1∶2.

Key words: cyclen, cationic lipid, spacer, gene vector