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Boron agents for neutron capture therapy
Coordination Chemistry Reviews ( IF 20.3 ) Pub Date : 2019-12-10 , DOI: 10.1016/j.ccr.2019.213139
Kuan Hu , Zhimin Yang , Lingling Zhang , Lin Xie , Lu Wang , Hao Xu , Lee Josephson , Steven H. Liang , Ming-Rong Zhang

Boron neutron capture therapy (BNCT) is a potential cancer radiotherapeutic modality, which takes advantage of the neutron capture response that occurs when boron (10B) is struck by low-energy thermal neutrons, triggering a nuclear fission reaction that ultimately causes cell death. Because the fatal radiation is restricted to approximately a single cell diameter, only cells with significant boron accumulation that are in the neutron field will be destroyed. Tumor-targeted 10B delivery agents are an essential component of BNCT. Currently, two low molecular weight boron-containing compounds, sodium mercaptoundecahydro-closo-dodecaborate (BSH) and borylphenylalanine (BPA), are mainly used in BNCT. Although both have suboptimal tumor selectivity, they have shown some therapeutic effect in patients with high-grade gliomas and several other kinds of tumors. In order to improve the efficacy of BNCT, significant effort has been devoted to developing new boron delivery agents that possess better uptake and favorable pharmacokinetic characteristics for clinical use. This review focuses on various boron delivery agents that have been developed over the past 40 years, including boron-containing amino acids, boron-containing compound conjugated-nucleosides, porphyrin derivatives, peptides, monoclonal antibodies, and different types of nanomaterials for 10B delivery. The principles underlying BNCT and the clinical trials with BNCT are briefly introduced in the first part of this review. In the second part, we provide a detailed overview of various boron delivery agents and discuss their merits and limitations. Additionally, the preclinical outcomes of these agents are included in this review and the most promising delivery agents are highlighted and compared. In summary, this article provides an overview of boron delivery agents, and critically analyzes their clinical prospects, from the view of medicinal chemists and nuclear medicine physicians.



中文翻译:

硼剂用于中子俘获治疗

硼中子俘获疗法(BNCT)是一种潜在的癌症放射治疗方式,它利用了低能热中子撞击硼(10 B)时发生的中子俘获反应,从而触发了核裂变反应,最终导致细胞死亡。因为致命辐射被限制在大约单个细胞直径,所以只有在中子场中具有大量硼积累的细胞才会被破坏。肿瘤靶向10B传递剂是BNCT的重要组成部分。当前,BNCT主要使用两种低分子量的含硼化合物,巯基癸二氢-十二碳酸钠(BSH)和硼基苯丙氨酸(BPA)。尽管两者对肿瘤的选择性都不理想,但它们在患有高级别神经胶质瘤和其他几种肿瘤的患者中已显示出一定的治疗效果。为了提高BNCT的功效,已经投入大量努力来开发新的硼递送剂,该硼递送剂具有更好的摄取和有利的临床药代动力学特性。这篇评论重点介绍了过去40年来开发的各种硼传递剂,包括含硼氨基酸,含硼化合物共轭核苷,卟啉衍生物,肽,单克隆抗体,10 B交货。本文的第一部分简要介绍了BNCT的基本原理以及使用BNCT进行的临床试验。在第二部分中,我们提供了各种硼输送剂的详细概述,并讨论了它们的优缺点。此外,这些药物的临床前结果也包括在本评价中,并突出显示和比较了最有希望的递送药物。总之,本文从药物化学家和核医学医师的角度概述了硼释放剂,并严格分析了它们的临床前景。

更新日期:2019-12-11
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