title: Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes.
abstract: Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes with MRI contrast properties. These compounds were designed to follow the biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with gadolinium were formed and characterized in terms of physicochemical and DNA binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was assayed in vitro on NIH 3T3. Different formulations of the product were tested. When up to 5% of the gadolinium lipid complexes were co-formulated with the cationic lipid RPR120535 used as a reference, the transfection levels were maintained as compared to RPR120535 alone. To date, only a liposomal formulation of a gadolinium-cationic lipid chelate without DNA had been observed using magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68-Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal. It was demonstrated that the new complexes also acted as transfection carriers when they were formulated from liposomes.
authors.affiliation: Bar Ilan University, Department of Chemistry, Laboratory of Peptidomimetics and Genetic Chemistry, 52900-Ramat Gan, Israel.
authors.forename: Francoise
authors.initials: F
authors.lastname: Leclercq
authors.forename: Mirit
authors.initials: M
authors.lastname: Cohen-Ohana
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.forename: Jean
authors.initials: J
authors.lastname: Herscovici
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Gerardo
authors.initials: G
authors.lastname: Byk
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media; D004247:DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005682:Gadolinium / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000628:therapy; D014018:Tissue Distribution; D014162:Transfection / Q000592:standards*; D014183:Transplantation, Heterologous
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D008055:Lipids; D008081:Liposomes; D004247:DNA; D005682:Gadolinium