Cationic Nucleoside Lipids for Gene Delivery

• Published in: Bioconjugate chemistry 2006-03, Vol.17 (2), p.466-472
• Main Authors: Chabaud, Pauline, Camplo, Michel, Payet, Dominique, Serin, Guillaume, Moreau, Louis, Barthélémy, Philippe, Grinstaff, Mark W
• Format: Article
• Language: English
• Subjects: Amino acids; Cations; Cations - chemistry; Cell Line, Tumor; Cell Proliferation; Cells; Ethidium; Ethidium - metabolism; Fatty Acids, Monounsaturated; Fatty Acids, Monounsaturated - chemistry; Fluorescent Dyes; Fluorescent Dyes - chemistry; Gene therapy; Gene Transfer Techniques; Humans; Immunology; Life Sciences; Lipids; Lipids - chemistry; Mammals; Molecular Structure; Nucleosides; Nucleosides - chemistry; Quaternary Ammonium Compounds; Quaternary Ammonium Compounds - chemistry; Uridine; Uridine - analogs & derivatives; Uridine - chemistry
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc050162q

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.