Targeting Hyperthermia for Renal Cell Carcinoma Using Human MN Antigenspecific Magnetoliposomes

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Abstract
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 Af–(6–maleimidocaproyl–oxy)–dipalmitoyl phosphatidylethanolamine (EMC–DPPE) in liposomal membrane. The targetabil–ity 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 tunes 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 tunes 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°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 hyper thermic treatment of carcinoma.