Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.
Magnetoliposomes (MLs) conjugated with an antibody fragment to give specificity to a tumor were applied to hyperthermia for cancer. The Fab' fragment of the G250 antibody, which binds to MN antigen on many types of human renal cell carcinoma, was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in liposomal membrane. The targetability of the G250-Fab' fragment-conjugating MLs (G250-FMLs) was investigated using the mouse renal cell carcinoma (mRCC) and MN antigen-presenting cell, MN-mRCC. The amount of G250-FMLs uptake reached 67 pg / cell against MN-mRCC cells in an in vitro experiment using plastic dishes and this value was about 6 times higher than that in the case of MLs. In an in vivo experiment using MN-mRCC-harboring mice, 1.5 mg of the FMLs per carcinoma tissue accumulated (tumor weight was 0.19 g), which corresponded to approximately 50% of the total injection. This value was 27 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using alternating magnetic field irradiation. The temperature of tumor tissue increased to 43 degrees C and the growth of the carcinoma was strongly arrested for at least 2 weeks. These results indicate the G250-FMLs could target renal cell carcinoma cells in vitro and in vivo, and are efficiently applicable to the hyperthermic treatment of carcinoma.
Shinkai
M
M
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo, Chikusa-ku, Nagoya 464-8603. takeshi@nubio.nagoya-u.ac.jp
Le
B
B
Honda
H
H
Yoshikawa
K
K
Shimizu
K
K
Saga
S
S
Wakabayashi
T
T
Yoshida
J
J
Kobayashi
T
T
D000818:Animals; D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D052203:Ferrosoferric Oxide; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007501:Iron / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008081:Liposomes / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008280:Magnetics / Q000627:therapeutic use; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D010087:Oxides / Q000008:administration & dosage* / Q000627:therapeutic use*; D016019:Survival Analysis; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D008081:Liposomes; D009363:Neoplasm Proteins; D010087:Oxides; D007501:Iron; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D052203:Ferrosoferric Oxide