title: Transfection with fluorinated lipoplexes based on new fluorinated cationic lipids and in the presence of a bile salt surfactant.
abstract: The synthesis of two fluorinated cationic lipids, which are analogues of frequently used synthetic gene carrier agents (including the cationic 2,3-dioleoyloxy-N-[2-(spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminium (DOSPA) component of the commercially available liposomal Lipofectamine), and the disintegration and DNA accessibility (evaluated by the ethidium bromide (BET) intercalation assay) as well as the in vitro transfection efficacy of cationic lipoplexes formulated with these new lipids in conjunction with conventional or fluorinated helper lipids, in the absence or presence of sodium taurocholate (STC), a powerful anionic bile salt detergent, is reported. A higher stability, with respect to the STC lytic activity and DNA accessibility, of the fluorinated cationic lipoplexes as compared with their respective lipofectamine-based ones was demonstrated. Indeed, while the Lipofectamine lipoplexes were fully disintegrated at a [STC]/[lipid] molar ratio of 2000, only 40-60% of the DNA intercalation sites of the lipoplexes based on the fluorinated analogue of DOSPA were accessible to ethidium bromide. A higher transfection potential in the presence of STC was further found for the lipoplexes formulated with the fluorinated analogue of DOSPA as compared with the Lipofectamine preparation. For a STC concentration of 7.5 mM, lipofection mediated with these fluorinated lipoplexes was significantly higher (nearly 30- to 50-fold, p < 0.05) than with the Lipofectamine ones. These results confirm the remarkable transfection potential of fluorinated lipoplexes.
authors.affiliation: Laboratoire de Chimie Bioorganique, UMR 6001 CNRS, Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Cédex 2, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Boulanger
authors.forename: Christophe
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gaucheron
authors.forename: Pierre
authors.initials: P
authors.lastname: Vierling
mesh_terms: D001647:Bile Acids and Salts / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D003902:Detergents / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D013096:Spermine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013501:Surface-Active Agents / Q000494:pharmacology*; D014162:Transfection / Q000295:instrumentation / Q000379:methods*
chemical_list: C098223:2,3-dioleyloxy-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethyl-1-propanaminium trifluoroacetate; D001647:Bile Acids and Salts; D002412:Cations; D003902:Detergents; D008055:Lipids; D013501:Surface-Active Agents; D005461:Fluorine; D013096:Spermine; D004247:DNA