Preparation of tumor-specific magnetoliposomes and their application for hyperthermia
Preparation of tumor-specific magnetoliposomes and their application for hyperthermia
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DOI：
10.1252/jcej.34.66
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发表时间：
2001-01-01
影响因子：
0.8
通讯作者：
Kobayashi, T
中科院分区：
文献类型：
--
作者：
Le, B;Shinkai, M;Kobayashi, T
磁性脂质体（MLs）与抗体片段偶联，对肿瘤具有特异性。抗体片段与N-（6-马来酰亚胺己丙氧基）-双棕榈酰磷脂酰乙醇胺（EMC-DPPE）交联在脂小体膜上。当EMC-DPPE的含量为10-wt%，固定反应时间为18 h时，固定抗体片段的效果最佳。Fab片段偶联命中数（FMLs）是全抗体固定方法的2.4倍。然后研究FMLs对胶质瘤细胞U251-SP的靶向性。在塑料培养皿的体外实验中，FMLs的摄取量达到85 pg/细胞。在一项以胶质瘤小鼠为实验对象的体内实验中，每1 g肿瘤组织累积260杯FMLs（肿瘤大小为0.1 cm(3)），相当于总注射量的约60%。这一数值是MLs的7倍。小鼠注射FMLs后，用交变磁场辐照进行细胞内热疗。肿瘤组织的温度升高到43度，肿瘤的生长在2周内被发现停止。这些结果表明，FMLs在体外和体内均能靶向胶质瘤细胞，可有效应用于肿瘤热疗。
Magnetoliposomes (MLs) were conjugated with an antibody fragment to give specificity to a tumor. The antibody fragment was cross-linked to N-(6-maleimidocaproyloxy)-dipalmitoyl phosphatidylethanolamine (EMC-DPPE) in tiposomal membrane. The immobilization of the antibody fragment was optimal when the content of EMC-DPPE was 10-wt% and the reaction time for immobilization was 18 h. The Fab' fragment-conjugating hits (FMLs) were 2.4 times higher molar immobilization density compared with the method using the whole antibody. The targetability of the FMLs to the glioma cells, U251-SP, was then investigated. The amount of FMLs uptake reached 85 pg/cell in an in vitro experiment using plastic dishes. In an in vivo experiment using glioma-harboring mice, 260 mug of the FMLs per 1 g of tumor tissue accumulated (tumor sizes was 0.1 cm(3)), which corresponded to approximately 60% of the total injection. This value was 7 times higher than that of the MLs. After injection of the FMLs, mice were exposed to intracellular hyperthermia using the alternating magnetic field irradiation. The temperature of tumor tissue increased to 43 degreesC and the growth of the tumor was found to be arrested over 2 weeks. These results indicate the FMLs could target the glioma cells in vitro and in vivo, and are efficiently applicable to the hyperthermia of tumor.