title: Lipothiophosphoramidates for gene delivery: critical role of the cationic polar headgroup.
abstract: When considering a family of cationic lipids designed for gene delivery, the nature of the cationic polar head probably has a great influence on both the transfection efficacy and toxicity. Starting from a cationic lipothiophosphoramidate bearing a trimethylammonium headgroup, we report herein the impact on gene transfection activity of the replacement of the trimethylammonium moiety by a trimethylphosphonium or a trimethylarsonium group. A series of three different human epithelial cell lines were used for the experimental transfection studies (HeLa, A549 and 16HBE14o(-)). The results basically showed that such structural modifications of the cationic headgroup can lead to a high transfection efficacy at low lipid/DNA charge ratios together with a low cytotoxicity. It thus appears that the use of a trimethylarsonium cationic headgroup for the design of efficient gene carriers, which was initially proposed in the lipophosphoramidate series, can be extended to other series of cationic lipids and might therefore have great potential for the development of novel non-viral vectors in general.
authors.affiliation: Université de Brest, Université Européenne de Bretagne, 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: Tony
authors.initials: T
authors.lastname: Le Gall
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Sevrain
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carmoy
authors.forename: Mattias F
authors.initials: MF
authors.lastname: Lindberg
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*; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry*; D014162:Transfection
chemical_list: D000577:Amides; D002412:Cations; D008055:Lipids; D008081:Liposomes; D010756:Phosphoric Acids; D004247:DNA; C011067:phosphoramidic acid