Receptor-mediated endocytosis of antibody-opsonized liposomes by tumor cells.
Specific receptor-mediated delivery of the contents of small, sonicated liposomes was studied with three murine tumor cell types: an IgG Fc receptor-negative nonphagocytic line (EL4); an Fc receptor-positive phagocytic line (P388D1); and an Fc receptor-positive nonphagocytic line (P388). The liposomes (formed from phosphatidylcholines, cholesterol, and dinitrophenyl-substituted phosphatidylethanolamine) contained carboxyfluorescein as a fluorescent marker and methotrexate as a pharmacologic agent. Binding and internalization of the liposomes were observed by fluorescence microscopy and measured by flow microfluorometry. The hapten-derivatized lipid was used as a binding point on the liposome for the antibody-combining site of the immunoglobulin. In the presence of IgG anti-dinitrophenyl, but not F(ab')2 or IgA anti-dinitrophenyl, liposomes bound to the Fc receptor-bearing cells. The liposomes underwent endocytosis by the P388D1 cells and, to a lesser extent, by the P388 cells. As measured by depression of [3H]deoxyuridine incorporation, methotrexate in IgG-opsonized liposomes had a much greater pharmacologic effect on the P388D1 cells than did the same amount in unopsonized liposomes or in free solution. This observation indicates that an appropriately chosen drug, incorporated in liposomes, can exert its effect on a cytoplasmic target after endocytosis. P388 cells showed a moderate effect of the drug in liposomes. Neither P388 nor P388D1 cells bound or ingested unopsonized liposomes, and the Fc receptor-negative EL4 line neither bound nor ingested opsonized liposomes. The data demonstrate specific interaction of opsonized liposomes with the cells' IgG Fc receptor.
D000818:Animals; D000906:Antibodies; D004705:Endocytosis; D005260:Female; D005455:Fluorescent Antibody Technique; D008081:Liposomes / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D009895:Opsonin Proteins; D011961:Receptors, Fc / Q000378:metabolism*
D000906:Antibodies; D008081:Liposomes; D009895:Opsonin Proteins; D011961:Receptors, Fc; D008727:Methotrexate