Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy
Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy
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来自碳硼烷安装的环状碳酸酯的两亲性聚碳酸酯作为硼中子捕获疗法的潜在试剂
DOI：
10.1021/acs.bioconjchem.6b00454
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发表时间：
2016
影响因子：
4.7
通讯作者：
Huang Yubin
中科院分区：
文献类型：
--
作者：
Xiong Hejian;Wei Xing;Zhou Dongfang;Qi Yanxin;Xie Zhigang;Chen Xuesi;Jing Xiabin;Huang Yubin
富硼碳硼烷在硼中子俘获治疗领域有着重要的应用。具有明确结构和可调硼原子负载的碳硼烷共轭聚合物的生物可降解衍生物远未被探索。本文通过碳硼烷嵌段环状碳酸酯单体的开环聚合，合成了一类新型的两亲性碳硼烷共轭聚碳酸酯。在聚乙二醇大分子引发剂的TBD催化下，聚合进行到相对高的转化率（>65%），在一定的分子量范围内具有低的多分散性。硼含量容易通过单体和引发剂的进料比来调节。所得的两亲性聚碳酸酯在水中自组装成不同尺寸的球形纳米颗粒，这取决于亲水性与疏水性的比率。研究表明，较大的纳米颗粒（PN150）更容易被蛋白质吸附并被肝脏捕获，而较小的纳米颗粒（PN50）更容易进入癌细胞并在肿瘤部位积聚。PN50与热中子照射表现出最高的治疗效果在体内。利用两亲性可生物降解的硼富集聚合物的新合成方法是有用的开发更有选择性和更有效的硼BNCT的输送系统。
Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.