Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy
Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy
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DOI：
10.1007/s11060-008-9522-8
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发表时间：
2008-05-01
影响因子：
3.9
通讯作者：
Miyatake, Shin-Ichi
中科院分区：
文献类型：
--
作者：
Doi, Atsushi;Kawabata, Shinji;Miyatake, Shin-Ichi
目的硼中子俘获治疗(BNCT)需要选择性地将高浓度的B-10(B-10)输送到肿瘤组织。为了改善BNCT中的药物传递，我们设计了转铁蛋白偶联聚乙二醇脂质体包裹硼酸钠(TF-PEG-BSH)。方法采用电感耦合等离子体原子发射光谱仪(ICPAES)测定3种含硼载体(裸BSH、PEGBSH和TFPEGBSH)对U87 Delta人脑胶质瘤细胞株B-10浓度的影响。用该细胞系进行克隆形成实验(CFA)，用3个BDS和中子照射。用免疫细胞化学方法检测肿瘤细胞中BSH的亚细胞定位。制作脑瘤模型，用电感耦合等离子体原子发射光谱仪分析肿瘤、血液和正常脑组织中的B-10浓度。评估肿瘤与血液的比值和肿瘤与正常脑组织的比值。对脑肿瘤模型进行BNCT检查，并分析其生存情况。结果在CFA中，在三种BDS中，Tf-PEG-BSH的中子照射效果最为显著。Tf-PEG-BSH在肿瘤组织中表现出高选择性和高效率的B-10传递。在处理实验中，TF-PEG-BSH组的存活率最高。免疫细胞化学显示，TF-PEG-BSH不仅能有效地将BSH送入细胞质，还能将BSH送入细胞核。结论TF-PEG-BSH不仅能将高浓度的B-10导入肿瘤组织，而且能选择性地将B-10导入肿瘤细胞，是一种有效的BNCT药物载体。
Object Boron neutron capture therapy (BNCT) requires selective delivery of a high concentration of boron-10 (B-10) to tumor tissue. To improve a drug delivery in BNCT, we devised transferrin-conjugated polyethylene-glycol liposome encapsulating sodium borocaptate (TF-PEG-BSH). Methods B-10 concentrations of U87 Delta human glioma cells from three boron delivery systems (BDS) (bare BSH, PEG-BSH, and TF-PEG-BSH) were analyzed in vitro by use of inductively coupled plasma-atomic emission spectrometry (ICP-AES). A colony-forming assay (CFA) was performed using this cell line with the three BDS and neutron irradiation. Subcellular localization of BSH in tumor cells was analyzed in vitro by immunocytochemistry using monoclonal antibodies raised for BSH. Brain tumor models were made and the B-10 concentrations of the tumor, blood, and normal brain from each BDS were analyzed in vivo by use of ICP-AES. The tumor-to-blood and the tumor-to-normal brain ratios were evaluated. BNCT for the brain tumor models was performed and survival was analyzed. Results In CFA, TF-PEG-BSH showed the most prominent effects by neutron irradiation among the three BDS. TF-PEG-BSH showed highly selective and highly efficient B-10 delivery in tumor tissue. The survival rate in the treatment experiment was best in the TF-PEG-BSH group. Immunocytochemically, TF-PEG-BSH delivered BSH efficiently not only into the cytoplasm but also into the nucleus. Conclusion TF-PEG-BSH is a potent BDS for BNCT not only in terms of delivering a high concentration of B-10 into tumor tissue, but also the selective delivery of B-10 into the tumor cells.