Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
Adv Mater. 2021 Feb;33(7):e2006892. doi: 10.1002/adma.202006892. Epub 2021 Jan 4.
Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H O ) into highly toxic hydroxyl radicals ( OH). To overcome the current limitations of the insufficient endogenous H O and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC-DOX) that possesses both H O self-supply and GSH-elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one-step biomineralization method using poly(ethylene glycol)-modified glucose oxidase (GOx) as a template to form biodegradable copper-doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H O , which not only starves the tumor cells, but also supplies H O for subsequent Fenton-like reaction. Meanwhile, the redox reaction between the released Cu ions and intracellular GSH will induce GSH depletion and reduce Cu to Fenton agent Cu ions, and then trigger the H O to generate OH by a Cu -mediated Fenton-like reaction, resulting in enhanced CDT efficacy. The integration of GOx-mediated starvation therapy, H O self-supply and GSH-elimination enhanced CDT, and DOX-induced chemotherapy, endow the PGC-DOX with effective tumor growth inhibition with minimal side effects in vivo.
化学动力学疗法（CDT）是一种通过将细胞内过氧化氢（H 2 O 2 ）转化为高毒性羟基自由基（OH）来杀死癌细胞的新兴治疗方法。为了克服目前内源性 H 2 O 2 不足和肿瘤细胞中谷胱甘肽（GSH）浓度过高的限制，提出了一种智能纳米催化治疗系统（记为 PGC-DOX），该系统具有 H 2 O 2 自供应和 GSH 消除特性，可实现高效的癌症治疗。该纳米平台是通过使用聚乙二醇（PEG）修饰的葡萄糖氧化酶（GOx）作为模板的简便一步生物矿化方法构建的，以形成可生物降解的铜掺杂磷酸钙纳米颗粒，然后负载阿霉素（DOX）。作为酶催化剂，GOx 可有效催化细胞内葡萄糖生成 H 2 O 2 ，不仅使肿瘤细胞饥饿，还为随后的芬顿样反应提供 H 2 O 2 。同时，释放的 Cu 离子与细胞内 GSH 之间的氧化还原反应会诱导 GSH 耗竭并将 Cu 还原为芬顿试剂 Cu 离子，然后通过 Cu 介导的芬顿样反应触发 H 2 O 2 生成 OH ，从而增强 CDT 疗效。GOx 介导的饥饿疗法、H 2 O 2 自供应和 GSH 消除增强 CDT 以及 DOX 诱导的化疗的结合，使 PGC-DOX 具有有效的肿瘤生长抑制作用，体内副作用最小。
