title: Cationic lipo-thiophosphoramidates for gene delivery: synthesis, physico-chemical characterization and gene transfection activity--comparison with lipo-phosphoramidates.
abstract: The synthesis of cationic lipo-thiophosphoramidates, a new family of cationic lipids designed for gene delivery, is reported herein. This new class of lipids is less polar than its oxygenated equivalent the lipo-phosphoramidates. Fluorescence anisotropy and FRET were used to determine the fluidity and fusogenicity of the lipo-phosphoramidates 3a-b and lipo-thiophosphoramidates 7a-b. The determination of both the size and the zeta potential of the nano-objects (liposomes and lipoplexes) and the determination of the DNA binding ability of the liposomes have completed the physico-chemical characterizations of the cationic lipids studied. Finally, the cationic lipids 3a-b and 7a-c have been evaluated as synthetic vectors for gene transfection into a variety of mammalian cell lines. The lipo-thiophosphoramidate 7a proved to be an efficient and low toxicity synthetic vector even when used at low lipid to DNA charge ratios.
authors.affiliation: Université Européenne de Bretagne, Université de Brest, CEMCA, CNRS UMR 6521, IFR 148 ScInBIoS, 6 Avenue Le Gorgeu, 29238 Brest, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Fraix
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carmoy
authors.forename: Damien
authors.initials: D
authors.lastname: Loizeau
authors.forename: Laure
authors.initials: L
authors.lastname: Burel-Deschamps
authors.forename: Tony
authors.initials: T
authors.lastname: Le Gall
authors.forename: Philippe
authors.initials: P
authors.lastname: Giamarchi
authors.forename: Hélène
authors.initials: H
authors.lastname: Couthon-Gourvès
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Haelters
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D016880:Anisotropy; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D015394:Molecular Structure; D013852:Thiotepa / Q000737:chemistry* / Q000494:pharmacology; D019076:Transgenes
chemical_list: D000577:Amides; D002412:Cations; D008081:Liposomes; D008567:Membranes, Artificial; D013852:Thiotepa