Influence of the galactosyl ligand structure on the interaction of galactosylated liposomes with mouse peritoneal macrophages.
Liposomes bearing at their surface mono- and triantennary galactosyl ligands were prepared and their interaction with the galactose receptor of mouse peritoneal macrophages studied. Triantennary structures were synthesized by coupling derivatives of 1-thio-beta-D-galactose to the amino groups of lysyl-lysine dipeptide. Galactosylated liposomes were obtained either by synthesis of neo-galactolipids followed by their incorporation into the vesicles or by neo-galactosylation of performed liposomes by reaction between thiol-functionalized galactosyl ligands and vesicles bearing maleimido groups. The interaction of the galactosylated liposomes with the macrophage lectin was remarkably sensitive to the topology of the ligands, i.e., a spacer-arm length about 3 nm was necessary and, in contrast to results obtained with the galactose receptor of other cells, the triantennary structure did not provide additional binding. Related to the strategy of drug delivery with targeted liposomes, these results indicate that lectins from different cells might possibly be distinguished by using multiantennary ligands having optimal geometries.
Haensler
J
J
Laboratoire de Chimie Bio-organique (CNRS URA 1386), Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
Schuber
F
F
D000818:Animals; D002240:Carbohydrate Sequence; D005690:Galactose / Q000737:chemistry*; D008024:Ligands; D008055:Lipids / Q000138:chemical synthesis; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010529:Peritoneal Cavity / Q000166:cytology*; D010743:Phospholipids / Q000138:chemical synthesis; D012276:Ricin / Q000737:chemistry; D013438:Sulfhydryl Compounds
D008024:Ligands; D008055:Lipids; D008081:Liposomes; D010743:Phospholipids; D013438:Sulfhydryl Compounds; D012276:Ricin; D005690:Galactose