Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy
Highly Condensed Boron Cage Cluster Anions in 2D Carrier and Its Enhanced Antitumor Efficiency for Boron Neutron Capture Therapy
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DOI：
10.1002/adfm.201704470
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发表时间：
2018-07-04
影响因子：
19
通讯作者：
Choy, Jin-Ho
中科院分区：
文献类型：
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作者：
Choi, Goeun;Jeon, Ie-Rang;Choy, Jin-Ho
在硼中子俘获治疗（BNCT）中，需要肿瘤细胞中有足够的硼才能成功给药，因此我们尝试将层状双氢氧化物（LDH）作为硼递送载体。为了满足这一要求，一种纳米杂化物（BSH-LDH），即LDH中的巯基十氢近十二硼酸盐（BSH）阴离子分子，作为硼的递送系统被开发出来。在U87胶质母细胞瘤细胞系中，BSH-LDH纳米颗粒（42.4 μ g B-10 -10（-6）细胞）渗透后的细胞硼含量大约是BNCT最低硼需求量（约0.02 μ g B-10 -10（-6）细胞）的2000倍，也比先前应用其他靶向策略的结果（0.2-1.5 μ g B-10 -10（-6）细胞）高出几个数量级。即使在低剂量（30 μ g B-10 mL(-1)）和弱辐照(1 × 10（12) n cm（-2）对应20 min）条件下，也能获得优异的中子捕获效率。根据异种移植小鼠模型的生物分布研究，在药物治疗后2小时内，BSH- ldh处理组BSH的肿瘤与血液比率比完整BSH处理组高4.4倍。目前BNCT联合硼递送系统为癌症治疗提供了一个有前景的综合治疗平台。
An attempt is made to apply layered double hydroxide (LDH) as a boron delivery carrier for boron neutron capture therapy (BNCT), which needs a sufficient amount of boron in tumor cells for its successful administration. To meet this requirement, a nanohybrid (BSH-LDH), mercaptoundecahydro-closo-dodecaborate (BSH) anionic molecules in LDH, is developed as a boron delivery system. The cellular boron content upon permeation of BSH-LDH nanoparticles (42.4 mu g B-10 10(-6) cells) in U87 glioblastoma cell line is found to be approximate to 2000 times larger than the minimum boron requirement (approximate to 0.02 mu g B-10 10(-6) cells) for BNCT and also orders of magnitude higher than the previous results (0.2-1.5 mu g B-10 10(-6) cells) by those applied with other targeting strategies, and eventually results in excellent neutron capture efficiency even under such low dose (30 mu g B-10 mL(-1)) and weak irradiation (1 x 10(12) n cm(-2) corresponding to 20 min) condition. According to the biodistribution studies in xenograft mice model, the tumor-to-blood ratio of BSH in the BSH-LDH-treated-group is found to be 4.4-fold higher than that in the intact BSH treated one in 2 h after drug treatment. The present BNCT combined with boron delivery system provides a promising integrative therapeutic platform for cancer treatment.