title: trans-2-Aminocyclohexanol-based amphiphiles as highly efficient helper lipids for gene delivery by lipoplexes.
abstract: Lipidic amphiphiles equipped with the trans-2-aminocyclohexanol (TACH) moiety are promising pH-sensitive conformational switches ("flipids") that can trigger a lipid bilayer perturbation in response to increased acidity. Because pH-sensitivity was shown to improve the efficiency of several gene delivery systems, we expected that such flipids could significantly enhance the gene transfection by lipoplexes. Thus a series of novel lipids with various TACH-based head groups and hydrocarbon tails were designed, prepared and incorporated into lipoplexes that contain the cationic lipid 1,2-dioleoyl-3-trimethylammonio-propane (DOTAP) and plasmid DNA encoding a luciferase gene. B16F1 and HeLa cells were transfected with such lipoplexes in both serum-free and serum-containing media. The lipoplexes consisting of TACH-lipids exhibited up to two orders of magnitude better transfection efficiency and yet similar toxicity compared to the ones with the conventional helper lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol. Thus, the TACH-lipids can be used as novel helper lipids for efficient gene transfection with low cytotoxicity.
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA; Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA; Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: nsamoshina@pacific.edu.
authors.forename: Nataliya M
authors.initials: NM
authors.lastname: Samoshina
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Vyacheslav V
authors.initials: VV
authors.lastname: Samoshin
authors.affiliation: Department of Chemistry, College of the Pacific, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Franz
authors.affiliation: Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 751 Brookside Road, Stockton, CA 95211, USA. Electronic address: xguo@pacific.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003511:Cyclohexanols / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008968:Molecular Conformation
chemical_list: C516358:2-aminocyclohexanol; D003511:Cyclohexanols; D008055:Lipids; D008156:Luciferases
keywords: Cationic liposome; Conformational switch; Gene delivery; Helper lipid; Transfection; pH-sensitive