Cationic lipids containing cyclen and ammonium moieties as gene delivery vectors.
In this study, two novel cationic lipids containing protonated cyclen and quaternary ammonium moieties were designed and synthesized as non-viral gene delivery vectors. The structures of the two lipids differ in their hydrophobic region (cholesterol or diosgenin). Cationic liposomes were easily prepared from the lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidylethanolamine. Several studies including DLS, gel retardation assay, and ethidium bromide intercalation assay suggest that these amphiphilic molecules are able to bind and compact DNA into nanometer particles which can be used as non-viral gene delivery agents. Our results from in vitro transfection show that in association with dioleoylphosphatidylethanolamine, two cationic lipids can induce effective gene transfection in human embryonic kidney 293 cells, although the gene transfection efficiencies of two cationic lipids were found to be lower than that of lipofectamine 2000(TM) . Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non-viral gene vectors.
Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610064, China.
Qing-Dong
QD
Huang
Jiang
J
Ren
Wen-Jing
WJ
Ou
Yun
Y
Fu
Mao-Qiang
MQ
Cai
Ji
J
Zhang
Wen
W
Zhu
Xiao-Qi
XQ
Yu
D002412:Cations / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D000080027:Cyclams; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D014162:Transfection
D002412:Cations; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008055:Lipids; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C038072:cyclen