Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.

Targeting hyperthermia for renal cell carcinoma using human MN antigen-specific magnetoliposomes.
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DOI:
10.1111/j.1349-7006.2001.tb01070.x
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发表时间:
2001-10
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Kobayashi T
Kobayashi T
中科院分区:
其他
文献类型:
--
作者:
Shinkai M;Le B;Honda H;Yoshikawa K;Shimizu K;Saga S;Wakabayashi T;Yoshida J;Kobayashi T

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与抗体片段缀合以提供对肿瘤的特异性的磁脂质体(ML)被应用于癌症的热疗。G250抗体的Fab'片段与许多类型的人肾细胞癌上的MN抗原结合,并与脂质体膜中的Af-(6-马来酰亚氨基己酰基-氧)-二棕榈酰磷脂酰乙醇胺(EMC-DPPE)交联。用小鼠肾细胞癌(mRCC)和MN抗原提呈细胞(MN-mRCC)研究了G250-Fab'片段偶联的MLs(G250-FML)的靶向性。在使用塑料培养皿的体外实验中,针对MN-mRCC细胞的G250-FML摄取量达到67 pg/细胞,该值比ML的情况高约6 μ g。在使用携带MN-mRCC的小鼠的体内实验中,每个癌组织累积了1.5mg的FML(肿瘤重量为0.19g),这相当于总注射量的约50%。这个值比ML的值高27个音调。在注射FML后,使用交变磁场照射将小鼠暴露于细胞内热疗。肿瘤组织的温度升高至43°C,并且癌的生长被强烈抑制至少2周。这些结果表明,G250-FML在体内外均能靶向肾癌细胞,可有效应用于肿瘤的热疗。
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.
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