Cytotoxicity of antibody-directed liposomes that recognize two receptors on K562 cells.
Encapsulation of methotrexate-gamma-aspartate in antibody-conjugated liposomes increased its toxicity for K562 cells, a human leukemia cell line that expresses Fc receptors and human glycophorin A. The liposomes were conjugated with either nonspecific mouse IgG, which interacts with an Fc receptor, or with monoclonal anti-human glycophorin, which interacts simultaneously with an Fc receptor and human glycophorin in the cell membrane. The drug in antibody-directed liposomes was up to 20 times more effective than the free drug, and it was 55 times more effective than the drug in liposomes bearing no surface ligand. The efficacy of drug delivery with liposomes directed only to an Fc receptor was reduced ninefold in the presence of soluble human IgG. Efficacy of drug delivery with liposomes directed both to the Fc receptor and to glycophorin A was not reduced by human IgG or soluble antiglycophorin A, but it was reduced twofold in the presence of both soluble ligands. These results were qualitatively consistent with previous studies on the binding of targeted liposomes to K562 cells.
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D006021:Glycophorins / Q000032:analysis*; D006801:Humans; D007074:Immunoglobulin G; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008081:Liposomes; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000633:toxicity; D011961:Receptors, Fc / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents; D006021:Glycophorins; D007074:Immunoglobulin G; D008081:Liposomes; D011961:Receptors, Fc; D012795:Sialoglycoproteins; C037394:methotrexate-gamma-aspartate; D008727:Methotrexate