Endocytosis does not necessarily augment the cytotoxicity of adriamycin encapsulated in immunoliposomes.

Abstract

We studied the relationship between endocytosis and cytoxicity of adriamycin (ADM) encapsulated in antibody-coated liposomes (immunoliposomes, IL) which are called chemoimmunoliposomes (CIL), by using several human cancer cell lines. IL coated with a monoclonal antibody, HBJ127 (IgG), which recognizes human gp125 antigen, specifically bound to gp125-positive target cancer cell lines, KU-1, T24, MKN-7, SKBr-3 and LS174T. Flow cytometric analysis using IL encapsulating carboxyfluorescein (CF) revealed that efficiencies of endocytosis varied among different cancer cells. The rate of IL internalization was in the order KU-1 > T24 > MKN-7 > SKBr-3 > LS174T. In 1 h incubation at 37 degrees C, all the four cell lines other than LS174T internalized about 60% of IL which were bound on their cell surfaces. KU-1, T24 and MKN-7, but not SKBr-3, significantly processed IL in endosome or lysosome. On the contrary, 80% of CIL bound to LS174T remained on the cell surface even after 2 h incubation. Furthermore, we evaluated the cytotoxic activities of CIL against the same panels of cancer cells. CIL inhibited the growth of all cancer cells tested in antibody-dependent manner, but, contrary to our expectation, KU-1 and T24 cells, which showed significant endocytosis activity, required a 7-14-fold higher amount of ADM binding than LS174T cells with low endocytosis activity for 50% cell growth inhibition. The difference of sensitivity to free ADM was only within 2.3-fold among those cancer cells. These results showing that liposomal ADM endocytosed is less effective than that remaining on the cell surface suggest that endocytosis is not necessarily required for cytotoxicity of CIL.

• Authors: S Suzuki, S Watanabe, S Uno, M Tanaka, T Masuko, Y Hashimoto
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1224 Issue 3 Pg. 445-53 (Dec 30 1994) ISSN: 0006-3002 [Print] Netherlands
• PMID: 7803502 (Publication Type: Journal Article)

Chemical References

• Antigens, Neoplasm
• Drug Carriers
• Liposomes
• Doxorubicin

Topics

• Antigens, Neoplasm (metabolism)
• Binding Sites
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage, pharmacology)
• Drug Carriers
• Endocytosis
• Humans
• Liposomes
• Tumor Cells, Cultured