State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, P. R. China.
Graduate School of Chinese Academy of Sciences , Beijing 100039, P. R. China.
Biomacromolecules. 2015 Dec 14;16(12):3980-8. doi: 10.1021/acs.biomac.5b01311. Epub 2015 Nov 23.
Carborane-conjugated amphiphilic copolymer nanoparticles were designed to deliver anticancer drugs for the combination of chemotherapy and boron neutron capture therapy (BNCT). Poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2(2-dicarba-closo-dodecarborane)propyloxycarbonyl-propyne carbonate) (PLMB) was synthesized via the versatile reaction between decaborane and side alkynyl groups, and self-assembled with doxorubicin (DOX) to form drug-loaded nanoparticles. These DOX@PLMB nanoparticles could not only suppress the leakage of the boron compounds into the bloodstream due to the covalent bonds between carborane and polymer main chains, but also protect DOX from initial burst release at physiological conditions because of the dihydrogen bonds between DOX and carborane. It was demonstrated that DOX@PLMB nanoparticles could selectively deliver boron atoms and DOX to the tumor site simultaneously in vivo. Under the combination of chemotherapy and BNCT, the highest tumor suppression efficiency without reduction of body weight was achieved. This polymeric nanoparticles delivery system could be very useful in future chemoradiotherapy to obtain improved therapeutic effect with reduced systemic toxicity.
硼烷共轭两亲性嵌段共聚物纳米粒子被设计用于递送抗癌药物，以结合化疗和硼中子俘获治疗（BNCT）。聚乙二醇-b-聚（L-丙交酯-co-2-甲基-2-(2-二碳硼烷-closo-十二硼烷)丙氧基羰基丙炔碳酸酯）（PLMB）通过硼烷与侧炔基之间的多功能反应合成，并与阿霉素（DOX）自组装形成载药纳米粒子。这些 DOX@PLMB 纳米粒子不仅由于硼烷和聚合物主链之间的共价键可以抑制硼化合物漏入血液，而且由于 DOX 和硼烷之间的氢键可以在生理条件下保护 DOX 免受初始突释。结果表明，DOX@PLMB 纳米粒子可以在体内选择性地将硼原子和 DOX 同时递送到肿瘤部位。在化疗和 BNCT 的联合作用下，实现了最高的肿瘤抑制效率，而体重没有减轻。这种聚合物纳米粒子输送系统在未来的化学放射治疗中可能非常有用，以获得改善的治疗效果，同时降低全身毒性。
