Liposomes coupled with monoclonal antibodies against glioma-associated antigen for targeting chemotherapy of glioma.
Liposomes have a variety of attributes as a drug delivery system. Targeting of liposomes to specific cells has been investigated by using appropriate cytophilic ligands such as monoclonal antibodies (MAb's). In the present study, liposomes with selective cytotoxicity toward glioma cells were obtained. An MAb which reacts with a glioma-associated antigen, G-22-MAb, was coupled with liposomes by the cross-linking reagent dipalmitoyl L-alpha-phosphatidylethanolamine 3-(2-pyridyldithio)propionate. Interaction of the liposomes with glioma cells was morphologically observed by fluorescence microscopy, and uptake of liposomal contents into glioma cells was analyzed by flow cytometry using carboxyfluorescein as a marker. It was demonstrated that G-22-MAb could be coupled with liposomes without altering its specificity toward glioma cells and that coupling with the MAb led to a significant increase in the uptake of liposomal contents into glioma cells. Liposomes containing an antitumor drug, methotrexate (MTX), were prepared and their cytotoxicity was examined by a colorimetric growth assay. Upon incorporation of MTX into the MAb-coupled liposomes, the cytotoxicity toward glioma cells was increased 100-fold as compared with free MTX. These results indicate that G-22-MAb-coupled liposomes containing MTX have selective cytotoxicity toward glioma cells and could be utilized for targeting the chemotherapy of gliomas.
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
A
A
Kito
J
J
Yoshida
N
N
Kageyama
N
N
Kojima
K
K
Yagi
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D008727:Methotrexate