title: Cyclen-based cationic lipids for highly efficient gene delivery towards tumor cells.
abstract: BACKGROUND
  Gene therapy has tremendous potential for both inherited and acquired diseases. However, delivery problems limited their clinical application, and new gene delivery vehicles with low cytotoxicity and high transfection efficiency are greatly required.
  
  
  METHODS
  In this report, we designed and synthesized three amphiphilic molecules (L1-L3) with the structures involving 1, 4, 7, 10-tetraazacyclododecane (cyclen), imidazolium and a hydrophobic dodecyl chain. Their interactions with plasmid DNA were studied via electrophoretic gel retardation assays, fluorescent quenching experiments, dynamic light scattering and transmission electron microscopy. The in vitro gene transfection assay and cytotoxicity assay were conducted in four cell lines.
  
  
  RESULTS
  Results indicated that L1 and L3-formed liposomes could effectively bind to DNA to form well-shaped nanoparticles. Combining with neutral lipid DOPE, L3 was found with high efficiency in gene transfer in three tumor cell lines including A549, HepG2 and H460. The optimized gene transfection efficacy of L3 was nearly 5.5 times more efficient than that of the popular commercially available gene delivery agent Lipofectamine 2000™ in human lung carcinoma cells A549. In addition, since L1 and L3 had nearly no gene transfection performance in normal cells HEK293, these cationic lipids showed tumor cell-targeting property to a certain extent. No significant cytotoxicity was found for the lipoplexes formed by L1-L3, and their cytotoxicities were similar to or slightly lower than the lipoplexes prepared from Lipofectamine 2000™.
  
  
  CONCLUSIONS
  Novel cyclen-based cationic lipids for effective in vitro gene transfection were founded, and these studies here may extend the application areas of macrocyclic polyamines, especially for cyclen.
authors: Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu, People's Republic of China.
authors: Qing-Dong
authors: QD
authors: Huang
authors: Guo-Xing
authors: GX
authors: Zhong
authors: Yang
authors: Y
authors: Zhang
authors: Jiang
authors: J
authors: Ren
authors: Yun
authors: Y
authors: Fu
authors: Ji
authors: J
authors: Zhang
authors: Wen
authors: W
authors: Zhu
authors: Xiao-Qi
authors: XQ
authors: Yu
mesh_terms: D002412:Cations; D016923:Cell Death; D045744:Cell Line, Tumor; D000080027:Cyclams; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004996:Ethidium / Q000378:metabolism; D018014:Gene Transfer Techniques; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008027:Light; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D012542:Scattering, Radiation; D055672:Static Electricity; D014162:Transfection
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D004247:DNA; C427203:calf thymus DNA; C038072:cyclen; D004996:Ethidium