Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron Neutron Capture Therapy
Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron Neutron Capture Therapy
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针对叶酸受体阳性肿瘤的硼中子俘获治疗的水溶性含近docecaborate翼基衍生物
DOI：
10.3390/cells9071615
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发表时间：
2020-07-01
期刊：
影响因子：
6
通讯作者：
Nakamura, Hiroyuki
中科院分区：
文献类型：
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作者：
Nakagawa, Fumiko;Kawashima, Hidehisa;Nakamura, Hiroyuki
开发了水溶性蝶酰-闭合-十二硼酸酯缀合物（PBMC 1-4）作为靶向硼中子捕获疗法（BNCT）的叶酸受体（FR α）的硼载体。PBMC 1-4具有足够低的细胞毒性，IC 50值在1至3 mM的范围内，对选定的人癌细胞，低到足以用作BNCT硼剂。PBMC 1-3显示FR α阳性细胞，特别是U87 MG胶质母细胞瘤细胞的显著细胞摄取，尽管PBC 4的积累与PBMC 1-3和L-4-硼苯丙氨酸（L-BPA）相比较低。通过增加培养基中叶酸的浓度，HeLa细胞对PBC 1和PBC 3的细胞摄取被阻止，表明PBC 1-3的主要摄取机制主要是通过FR α受体介导的内吞作用。
Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1-4), were developed as folate receptor (FR alpha) targeting boron carriers for boron neutron capture therapy (BNCT). PBCs 1-4 had adequately low cytotoxicity with IC50 values in the range of 1 similar to 3 mM toward selected human cancer cells, low enough to use as BNCT boron agents. PBCs 1-3 showed significant cell uptake by FR alpha positive cells, especially U87MG glioblastoma cells, although the accumulation of PBC 4 was low compared with PBCs 1-3 and L-4-boronophenylalanine (L-BPA). The cellular uptake of PBC 1 and PBC 3 by HeLa cells was arrested by increasing the concentration of folate in the medium, indicating that the major uptake mechanisms of PBC 1-3 are primarily through FR alpha receptor-mediated endocytosis.