Preparation of neo-galactosylated liposomes and their interaction with mouse peritoneal macrophages.
In order to target liposomes to cells expressing at their surface a galactose-binding site we have prepared liposomes containing new synthetic galactolipids. Neo-galactosylated liposomes were prepared by covalently coupling beta-D-1-thiogalactopyranoside residues, substituted with a hydrophilic spacer-arm and functionalized with a sulfhydryl group, to preformed large unilamelar vesicles containing 4-(p-maleimidophenyl)butyryl phosphatidylethanolamine. The vesicles, having a galactose content above a threshold value of about 5 mol%, could be aggregated with Ricinus communis agglutinin. This aggregation was reversed by addition of excess free methyl beta-D-galactopyranoside, indicating that the surface glucidic moieties of these liposomes were accessible to the lectin. Compared to the control vesicles, the neo-galactosylated liposomes (containing 15 mol% galactose) presented in vitro an increased binding to cell possessing a beta-D-galactose specific receptor, i.e. resident mouse peritoneal macrophages. At 4 degrees C, the specific binding was about 2-fold, whereas at 37 degrees C it was increased to about 4-5-fold. This differential binding was largely unaffected by serum and, interestingly was much dependent on the degree of galactosylation of the liposomes, i.e. a threshold value of 5 mol% was needed to observe an increased binding of the targeted vesicles to the macrophages.
Haensler
J
J
Laboratoire de Chimie Enzymatique (CNRS UA 1182), Université Louis Pasteur, Institut de Botanique, Strasbourg, France.
Schuber
F
F
D000818:Animals; D001202:Ascitic Fluid; D055598:Chemical Phenomena; D002621:Chemistry; D003080:Cold Temperature; D038983:Galactolipids; D006017:Glycolipids; D037102:Lectins / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D037121:Plant Lectins; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship
D038983:Galactolipids; D006017:Glycolipids; D037102:Lectins; D008081:Liposomes; D037121:Plant Lectins; D011956:Receptors, Cell Surface; C017707:Ricinus communis agglutinin-1; C039707:galactose receptor