title: A novel cationic lipophosphoramide with diunsaturated lipid chains: synthesis, physicochemical properties, and transfection activities.
abstract: Cationic lipophosphoramidates constitute a class of cationic lipids we have previously reported to be efficient for gene transfection. Here, we synthesized and studied a novel lipophosphoramidate derivative characterized by an arsonium headgroup linked, via a phosphoramidate linker, to an unconventional lipidic moiety consisting of two diunsaturated linoleic chains. Physicochemical studies allowed us to comparatively evaluate the specific fluidity and fusogenicity properties of the liposomes formed. Although corresponding lipoplexes exhibited significant but relatively modest in vitro transfection efficiencies, they showed a remarkably efficient and reproducible ability to transfect mouse lung, with in vivo transfection levels higher than those observed with a monounsaturated analogue previously described. Thus, these results demonstrate that this diunsaturated cationic lipophosphoramidate constitutes an efficient and versatile nonviral vector for gene transfection. They also invite further evaluations of the transfection activity, especially in vivo, of gene delivery systems incorporating the lipid reported herein and/or other lipids bearing polyunsaturated chains.
authors.affiliation: INSERM U613, Université de Bretagne Occidentale, Brest, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Le Gall
authors.forename: Damien
authors.initials: D
authors.lastname: Loizeau
authors.forename: Erwan
authors.initials: E
authors.lastname: Picquet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carmoy
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Yaouanc
authors.forename: Laure
authors.initials: L
authors.lastname: Burel-Deschamps
authors.forename: Pascal
authors.initials: P
authors.lastname: Delépine
authors.forename: Philippe
authors.initials: P
authors.lastname: Giamarchi
authors.forename: Paul-Alain
authors.initials: PA
authors.lastname: Jaffrès
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D016880:Anisotropy; D001152:Arsenicals / Q000737:chemistry; D002412:Cations; D002460:Cell Line; D003102:Colloids; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008041:Linoleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010756:Phosphoric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014162:Transfection; D019076:Transgenes
chemical_list: D000577:Amides; D001152:Arsenicals; D002412:Cations; D003102:Colloids; D008041:Linoleic Acids; D008081:Liposomes; D010756:Phosphoric Acids; D004247:DNA; C011067:phosphoramidic acid; D008156:Luciferases