Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy
Bcl-2 inhibitor uploaded upconversion nanophotosensitizers to overcome the photodynamic therapy resistance of cancer through adjuvant intervention strategy
复制标题
Bcl-2抑制剂上传上转换纳米光敏剂通过辅助干预策略克服癌症光动力治疗耐药
DOI：
10.1016/j.biomaterials.2017.08.010
复制
发表时间：
2017-11-01
期刊：
影响因子：
14
通讯作者：
Kong, Xianggui
中科院分区：
文献类型：
--
作者：
Liu, Xiaomin;Fan, Zhongqi;Kong, Xianggui
与许多其他抗癌疗法类似，光动力疗法（PDT）也遭受由细胞存活途径介导的内在癌症抗性。这些生存途径受多种蛋白的调控，其中抗凋亡蛋白Bcl-2在细胞程序性死亡的调控中起重要作用，并已被证实参与抗氧化刺激的保护作用。面对这一挑战，我们提出并验证了一种新的上转换光敏纳米平台，它可以显着降低癌症的耐药性，提高PDT的疗效。上转换纳米光敏剂含有光敏分子-酞菁锌（ZnPc）和Bcl-2抑制剂-ABT 737小分子，表示为ABT 737 @ ZnPc-UCNP。以pH敏感的方式，通过聚（乙二醇）-聚（L-组氨酸）二嵌段共聚物（PEG-b-PHis）将ABT 737分子包封到纳米平台中。该纳米系统通过辅助干预策略表现出对肿瘤细胞进行PDT增敏的优势。当到达溶酶体时，酸性环境改变了PEG-b-PHis的溶解度，导致ABT 737分子的爆发式释放，这耗尽了肿瘤细胞中的Bcl-2水平，使肿瘤细胞提前脱离抗凋亡存活途径的保护。由于ABT 737 @ZnPc-UCNPs的敏化作用，可以在体外和体内显著增强癌细胞的PDT治疗效率。(C)2017由Elsevier Ltd.出版
Similar to many other anticancer therapies, photodynamic therapy (PDT) also suffers from the intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by various proteins, among which anti-apoptotic protein Bcl-2 plays an important role in regulation of programmed cell death and has been proved to involve in protecting against oxidative stimuli. Confronted by this challenge, we propose and validate here a novel upconversion photosensitizing nanoplatform which enables significant reduction of cancer resistance and improve PDT efficacy. The upconversion nano-photosensitizer contains the photosensitizing molecules - Zinc phthalocyanine (ZnPc) and Bcl-2 inhibitor - ABT737 small molecules, denoted as ABT737@ZnPc-UCNPs. ABT737 molecules were encapsulated, in a pH sensitive way, into the nanoplatform through Poly (ethylene glycol)-Poly (L-histidine) diblock copolymers (PEG-b-PHis). This nanosystem exhibits the superiority of sensitizing tumor cells for PDT through adjuvant intervention strategy. Upon reaching to lysosomes, the acidic environment changes the solubility of PEG-b-PHis, resulting in the burst-release of ABT737 molecules which deplete the Bcl-2 level in tumor cells and leave the tumor cells out from the protection of anti-apoptotic survival pathway in advance. Owing to the sensitization effect of ABT737@ZnPc-UCNPs, the PDT therapeutic efficiency of cancer cells can be significantly potentiated in vitro and in vivo. (C) 2017 Published by Elsevier Ltd.