In vitro cytotoxic study of immunoliposomal doxorubicin targeted to human CD34(+) leukemic cells.
The expression of CD34 antigen in acute myelogenous leukemias is considered an unfavourable prognosis marker for response to anticancer drugs and duration of remission. This study investigated the applicability of long-circulating immunoliposomes loaded with doxorubicin targeted to CD34 antigen present on MDR(+) human myelogenous leukemia KG-1a cell line. Immunoliposomal doxorubicin showed a higher cytotoxicity against KG-1a cells than non-targeted liposomal doxorubicin, but it did not improve over that of free drug. Although no reversal of doxorubicin resistance was found to occur through its liposomal encapsulation, a therapeutic benefit can be obtained by the selective cytotoxicity observed. Endocytosis studies demonstrated that, after binding to CD34 antigen, the immunoliposomes are not internalized by the KG-1a cells and so the cytotoxic effect might be due to drug released into the space near the cell membrane. Thus, immunotargeting of liposomal doxorubicin to CD34(+) leukemic cells may only provide an ex vivo strategy for site-selective CD34(+) leukemia cell killing.
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Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona. Martí i Franqués 1, 08028 Barcelona, Spain.
de Madariaga
M A
MA
Domingo
J C
JC
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000276:immunology*; D002214:Capsules; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007120:Immunochemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes; D018613:Microscopy, Confocal; D010316:Particle Size
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D002214:Capsules; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin