Web Release Date: February 8,
Cationic Nucleoside Lipids for Gene Delivery
and
Groupe de Chimie Organique et des Matériaux Moléculaires (UMR-CNRS 6114), Faculté des Sciences de Luminy, case 901, 13288 Marseille Cedex 09, France, INSERM U386, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat 33076 Bordeaux Cedex, France, Laboratoire de Chimie Biologique UMR A408 Faculté des sciences d'Avignon 33, rue Louis Pasteur, 84000 Avignon, France, Centre d'Immunologie de Marseille Luminy, Parc scientifique de Luminy, 13288 Marseille, Cedex 9, France, Oncodesign, Parc de la Toison d'Or, 28 rue Louis de Broglie, 21000 Dijon, France, and Departments of Biomedical Engineering and Chemistry, Boston University, Boston, Massachusetts 02215
Received June 7, 2005
Revised January 4, 2006
Abstract:
A novel uridine-based nucleo-lipid, DOTAU (N-[5'-(2',3'-dioleoyl)uridine]-N',N',N'-trimethylammonium tosylate) was prepared by using a convenient four-step synthetic pathway. From the preliminary physicochemical studies (quasielastic light scattering and light microscopy), this amphiphilic structure forms supramolecular organizations in aqueous solution. In addition, in the presence of nucleic acids, transmission electronic microscopy experiments (TEM) and small angle X-ray scattering (SAXS) reveal the formation of multilamellar structures similar to lipoplexes (cationic liposome-DNA complexes) with cationic lipids. The formation of a complex was confirmed by fluorescence spectroscopic assays involving ethidium bromide. Transfection assays of mammalian cell lines (HeLa and MCF-7) indicate that DOTAU can transfect efficiently an expression vector (pEGFP) encoding GFP. Proliferation assays realized on these cell lines show that DOTAU does not inhibit cell proliferation and is less toxic than the commercial Lipofectamine 2000.
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