Sterically stabilized anti-G(M3), anti-Le(x) immunoliposomes: targeting to B16BL6, HRT-18 cancer cells.
Various tumor-associated antigens have been identified as carbohydrates bound to lipids or to proteins expressed on tumor cell membranes. We prepared tumor-specific immunoliposomes by coupling anticarbohydrate antibodies, such as antiganglioside G(M3) antibody (DH2) or anti-Le(x) antibody (SH1), to polyethylene glycol (PEG)-coated liposomes. In vitro and in vivo targetability of anti-G(M3) and anti-Le(x) immunoliposomes to B16BL6 mouse melanoma cells and HRT-18 human colorectal adenocarcinoma cells were monitored with a fluorescence microscopy, and analyzed by biodistribution assay of the immunoliposome in mice bearing the tumor tissues. The antibody coupling to the PEG liposomes did not greatly diminish the circulation time of the liposome in the C57BL/6 mouse model. In vitro cytotoxicity of doxorubicin encapsulated in liposomes was enhanced by antibody coupling, but still behind free doxorubicin. However, in vivo antitumor therapeutic efficacy of doxorubicin encapsulated in the immunoliposomes was far greater than the free drug or in conventional liposomes. Doxorubicin encapsulated in anti-G(M3) immunoliposomes was able to reduce in vivo tumor growth and metastasis of B16BL6 mouse melanoma cells more greatly than any other formulations of the drug. This study suggests that tumor-associated antigens can be good target molecules for tumor-specific delivery of liposomal drugs or other synthetic drug delivery systems.
Nam
S M
SM
Department of Medical Technology, Yonsei University, Wonju, Republic of Korea.
Kim
H S
HS
Ahn
W S
WS
Park
Y S
YS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D005679:G(M3) Ganglioside / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D016256:Lewis X Antigen / Q000276:immunology*; D008081:Liposomes; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy; D051379:Mice; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005679:G(M3) Ganglioside; D000922:Immunotoxins; D016256:Lewis X Antigen; D008081:Liposomes; D004317:Doxorubicin