Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro.
Liposome entrapment of doxorubicin has been shown to reduce its cardiotoxicity in vivo and increase its therapeutic index. A further improvement in therapeutic index could be achieved through targeting of liposome-entrapped drug selectively to cancer cells. Monoclonal antibodies against the squamous lung cancer cell line KLN-205 have been ligated to the surface of long-circulating (Stealth) and conventional liposomes. The antibody-bearing liposomes showed specific, competitive uptake by KLN-205 cells as compared to liposomes bearing nonspecific isotype-matched antibodies or antibody-free liposomes. Doxorubicin-containing antibody-liposomes resulted in as much as a 15-fold decrease in the 50% inhibitory concentration for doxorubicin against KLN-205 cells as compared to free doxorubicin or doxorubicin entrapped in antibody-free liposomes.
Ahmad
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Department of Pharmacology, University of Alberta, Edmonton, Canada.
Allen
T M
TM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D001692:Biological Transport; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D000922:Immunotoxins / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D008081:Liposomes; D004317:Doxorubicin