Neo-mannosylated liposomes: synthesis and interaction with mouse Kupffer cells and resident peritoneal macrophages.
In order to target liposomes to cells expressing at their surface mannose receptors, e.g. mouse Kupffer cells and peritoneal macrophages, we have developed a new synthetic strategy which allows a chemically well defined preparation of neo-mannosylated vesicles. alpha-D-Thiomannopyranoside residues, substituted with a hydrophilic spacer arm and functionalized with a sulfhydryl group, were covalently coupled to preformed large unilamellar vesicles containing 4-(p-maleimidophenyl)butyryl phosphatidylethanolamine. Liposomes, containing 15 mol% of mannosyl residues, were specifically aggregated with concanavalin A; this aggregation could be reversed by an excess of free methyl alpha-D-mannopyranoside indicating that the surface ligands were freely accessible to the lectin. The neo-mannosylated liposomes presented in vitro an increased binding to cells possessing alpha-D-mannose specific binding sites. At 37 degrees C a specific binding, up to 9-fold compared to control vesicles, was observed. These neo-mannosylated vesicles represent attractive tools for targeting bio-active molecules to macrophage-associated diseases.
Muller
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Laboratoire de Chimie Enzymatique, CNRS UA 1182, Université Louis Pasteur, Strasbourg, France.
Schuber
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D000818:Animals; D003208:Concanavalin A; D007202:Indicators and Reagents; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology*; D037181:Lectins, C-Type; D008081:Liposomes / Q000138:chemical synthesis* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D015394:Molecular Structure; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*
D007202:Indicators and Reagents; D037181:Lectins, C-Type; D008081:Liposomes; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D003208:Concanavalin A; D008358:Mannose