State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry , Chinese Academy of Sciences , Changchun 130022 , PR China.
University of Science and Technology of China , No. 96, JinZhai Road , Baohe District, Hefei , Anhui 230026 , P. R. China.
ACS Appl Mater Interfaces. 2019 Sep 4;11(35):31671-31680. doi: 10.1021/acsami.9b10685. Epub 2019 Aug 21.
Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment, which severely hinders cancer treatments. Here, we design a novel biodegradable therapeutic system, O-Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O-enhanced combination therapy. Notably, the doped Cu doubles the O storage capacity of the ZIF-8 matrix, which makes OCZCF an excellent pH-sensitive O reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of chlorin e6 (Ce6) under 650 nm laser irradiation. Moreover, the released Cu can act as a smart reactive oxygen species protector by consuming intracellular GSH. The byproduct Cu will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant HO. The accompanying O will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.
缺氧和谷胱甘肽（GSH）的过表达是肿瘤微环境的典型特征，严重阻碍了癌症治疗。在这里，我们设计了一种新型的可生物降解治疗系统，O-Cu/ZIF-8@Ce6/ZIF-8@F127（OCZCF），以同时实现 GSH 耗竭和 O 增强的联合治疗。值得注意的是，掺杂的 Cu 使 ZIF-8 基质的 O 储存能力增加了一倍，这使得 OCZCF 成为一种出色的 pH 敏感 O 储存库，可克服肿瘤缺氧，增强氯乙酮（Ce6）在 650nm 激光照射下的光动力治疗（PDT）效率。此外，释放的 Cu 可以通过消耗细胞内 GSH 作为智能活性氧保护剂。在有大量 HO 的情况下，副产物 Cu 将经历高效的芬顿样反应以实现化学动力学治疗（CDT）。伴随的 O 将进一步缓解缺氧。体外和体内实验数据表明，OCZCF 可以通过增强协同 PDT 和 CDT 引起显著的肿瘤抑制作用，这可能为癌症治疗开辟新途径。
