title: High transfection efficiency of cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails.
abstract: The ability of a nonviral gene delivery system to overcome extra- and intracellular barriers is a critical issue for the future clinical applications of gene therapy. In recent years much effort has been focused on the development of a variety of DNA carriers, and cationic liposomes have become the most common nonviral gene delivery system. One hundred and eighty novel cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails were synthesized by parallel solid-phase chemistry. The liposomes were prepared and gel retardation assays were used to study the binding efficiency between the prepared liposome and the DNA. Transfection efficiencies of the lipids were evaluated against various mammalian cells, such as human embryonic kidney (HEK293), human cervical adenocarcinoma (HeLa), canine osteosarcoma (D17), colorectal adenocarcinoma (COLO 205), and human prostate adenocarcinoma (PC3) cells. The lipids with an acyl portion at the terminal part of the polyamine backbone exhibited higher transfection efficiency than those with the acyl portion as an internal part of the backbone. These compounds also showed higher transfection efficiency and lower cytotoxicity than the commercially available agents, Effectene, DOTAP, and DC-Chol.
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkapi, Bangkok 10240, Thailand.
authors.forename: Widchaya
authors.initials: W
authors.lastname: Radchatawedchakoon
authors.forename: Aungkana
authors.initials: A
authors.lastname: Krajarng
authors.forename: Nattisa
authors.initials: N
authors.lastname: Niyomtham
authors.forename: Ramida
authors.initials: R
authors.lastname: Watanapokasin
authors.forename: Boon-ek
authors.initials: BE
authors.lastname: Yingyongnarongkul
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008081:Liposomes / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D014162:Transfection
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D004247:DNA; D002784:Cholesterol