Antibody-targeted liposomes: increase in specific toxicity of methotrexate-gamma-aspartate.
Liposomes conjugated with anti-H2Kk antibody associate with L929 murine fibroblasts in 6- to 20-fold greater amount than do nonspecific liposomes. The ability of methotrexate-gamma-aspartate to inhibit L929 growth is increased 10-fold when encapsulated in targeted liposomes but is decreased to 50% when encapsulated in liposomes with no specificity for the target cells. Ammonium chloride inhibits the effects of the encapsulated but not the free drug. Soluble antibody does not inhibit the efficacy of targeted vesicles, but empty targeted vesicles do inhibit the efficacy. The compound in both targeted and nontargeted vesicles has a minimal effect on BALB/c3T6 fibroblasts. These results demonstrate the potential of antibody-targeted liposomes and the importance of selecting liposome-dependent cytotoxic agents.
D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage*; D008285:Major Histocompatibility Complex; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D008081:Liposomes; C037394:methotrexate-gamma-aspartate; D008727:Methotrexate