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 pres...

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Bibliographic Details
Published in:Life sciences (1973) 2004-06, Vol.75 (3), p.313-328
Main Authors: Carrion, C, de Madariaga, M.A, Domingo, J.C
Format: Article
Language:English
Subjects:
Acute myelogenous leukemia
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Antibiotics, Antineoplastic - pharmacology
Antibodies, Monoclonal
Antigens, CD34 - immunology
Capsules
CD34 antigen
Cell Division
Cell Line, Tumor
Cell Survival - drug effects
Chemistry, Pharmaceutical
Doxorubicin - administration & dosage
Doxorubicin - pharmacokinetics
Doxorubicin - pharmacology
Drug Carriers
Drug Delivery Systems
Endocytosis - drug effects
Flow Cytometry
Humans
Immunochemistry
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - pathology
Liposomal doxorubicin
Liposomes
Microscopy, Confocal
Particle Size
Sterically stabilized immunoliposomes
Targeted drug delivery
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Summary: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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2003.12.020