title: Lipophosphoramidate-based bipolar amphiphiles: their syntheses and transfection properties.
abstract: Six new cationic bolaamphiphiles (also called bipolar amphiphiles, bolaform amphiphiles, or bolalipids) were readily prepared by a thiol-ene click reaction that engaged a mercapto-alcohol (mercapto-ethanol or mercapto-hexanol) and a cationic based lipophosphoramidate. The cationic lipophosphoramidates contain two lipid chains that end in an alkene group and a selected cationic polar head group (trimethylammonium, dimethyl hydroxyethyl ammonium, or methylimidazolium). These compounds were formulated in water (with or without DOPE as a colipid) to produce supramolecular aggregates. These aggregates, before (i.e. bolasomes) and after (i.e. bolaplexes) mixing with plasmid DNA (pDNA) at various charge ratios, were characterized with regard to their sizes and zeta potentials. In the case of bolasomes, the suspensions were unstable since precipitation occurred after only a few hours at room temperature. On the other hand, bolaplex formulations exhibited clearly a better colloidal stability. Then, the gene delivery properties of the cationic bolasomes were investigated using two human-derived epithelial cell lines (A549 and 16HBE). Compared to the commercially available lipofection reagent (Lipofectamine), most of the cationic bolaamphiphiles were able to efficiently transfect these cells when they were formulated with DOPE in a 1 : 1 molar ratio. We report herein that bolaamphiphiles possessing a trimethylammonium or a dimethyl hydroxyethyl ammonium head group were the most efficient in terms of transfection efficiency while exhibiting no significant cytotoxicity.
authors: UMR CNRS 6521 Université de Brest, IBSAM, Faculté des Sciences, 6 avenue Victor Le Gorgeu, 29238 Brest, France. mathieu.berchel@univ-brest.fr and IBiSA SynNanoVect Platform, IBSAM, Université de Bretagne Occidentale, 29238 Brest Cedex 3, France.
authors: Mathieu
authors: M
authors: Berchel
authors: Unité INSERM 1078, IBSAM, Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, 22 avenue Camille Desmoulins, 29328 Brest, France and IBiSA SynNanoVect Platform, IBSAM, Université de Bretagne Occidentale, 29238 Brest Cedex 3, France.
authors: Tony
authors: T
authors: Le Gall
authors: UMR CNRS 6521 Université de Brest, IBSAM, Faculté des Sciences, 6 avenue Victor Le Gorgeu, 29238 Brest, France. mathieu.berchel@univ-brest.fr.
authors: Olivier
authors: O
authors: Lozach
authors: UMR CNRS 6521 Université de Brest, IBSAM, Faculté des Sciences, 6 avenue Victor Le Gorgeu, 29238 Brest, France. mathieu.berchel@univ-brest.fr.
authors: Jean-Pierre
authors: JP
authors: Haelters
authors: Unité INSERM 1078, IBSAM, Université de Bretagne Occidentale, Faculté de Médecine et des Sciences de la Santé, 22 avenue Camille Desmoulins, 29328 Brest, France and IBiSA SynNanoVect Platform, IBSAM, Université de Bretagne Occidentale, 29238 Brest Cedex 3, France and CHRU de Brest, Service de Génétique Moléculaire et d'Histocompatibilité, 5 avenue du Maréchal Foch, 29609 Brest cedex, France and DUMG, Faculté de Médecine et des Sciences de la Santé, 22 avenue Camille Desmoulins, 29328 Brest, France.
authors: Tristan
authors: T
authors: Montier
authors: UMR CNRS 6521 Université de Brest, IBSAM, Faculté des Sciences, 6 avenue Victor Le Gorgeu, 29238 Brest, France. mathieu.berchel@univ-brest.fr and IBiSA SynNanoVect Platform, IBSAM, Université de Bretagne Occidentale, 29238 Brest Cedex 3, France.
authors: Paul-Alain
authors: PA
authors: Jaffrès
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D014162:Transfection
chemical_list: D000577:Amides; D008055:Lipids; D010756:Phosphoric Acids; C011067:phosphoramidic acid