title: Novel galactosylated polyamine bolaamphiphiles for gene delivery.
abstract: We describe the synthesis of a series of alpha-galacto-omega-polyamine double-chain bolaamphiphiles (Gal-CL) and report on the gene transfer mediated with lipoplexes they form either when used in conjunction with DOPE or with pcTG90:DOPE. Lipofection was investigated with human HepG2 and murine BNL-CL2 hepatocytes expressing the asialoglycoprotein (ASGP) receptor which displays a high affinity for galactosyl residues, and with A549 cells which do not express ASGP. Our results show that cationic N/P = 5 and 2.5 Gal-CL lipoplexes constitute very efficient nonspecific gene transfer systems. Lipofection experiments performed in the presence of asialofetuin (a high affinity ligand of ASGP) led us to evidence also the involvement of a specific receptor-mediated endocytosis pathway for the transfection of the ASGP(+) HepG2 or BNL-CL2 hepatocytes with some Gal-CL formulations. This work suggests that targetable lipopolyamines presenting a single galactose residue appear as promising synthetic vectors for specific gene delivery to ASGP(+) cells.
authors.affiliation: Laboratoire de Chimie Bioorganique, UMR 6001 CNRS-Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Nice Cédex 2, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Fabio
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gaucheron
authors.forename: Christophe
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Pierre
authors.initials: P
authors.lastname: Vierling
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000096:biosynthesis; D002470:Cell Survival; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D008027:Light; D008156:Luciferases / Q000235:genetics; D051379:Mice; D009005:Monosaccharides / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D011073:Polyamines / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection; D019076:Transgenes / Q000235:genetics
chemical_list: D037263:Asialoglycoprotein Receptor; D007202:Indicators and Reagents; D009005:Monosaccharides; D011073:Polyamines; C478640:alpha-galacto-omega-polyamine; D008156:Luciferases