化学动力学疗法（CDT）受到肿瘤微环境的限制，例如低浓度的过氧化氢（H2O2）。增加H2O2的治疗策略与CDT相结合可以协同增强治疗效果。在此，开发了一种新型超分子 PEG-DNA-二茂铁纳米凝胶，可以同时传递葡萄糖氧化酶（GOx）和缺氧激活的前药替拉扎明（TPZ），通过级联反应协同放大 CDT。 DNA 纳米凝胶尺寸可控，具有 DNase I 响应性，并表现出良好的生物相容性。在GOx催化反应中耗氧和生成H2O2的诱导下，纳米凝胶中的药物TPZ和二茂铁分别发生缺氧反应和芬顿反应。体外模型试验、细胞内ROS测试、MTT实验和DNA损伤实验表明，基于H2O2的级联Fenton反应和基于缺氧的级联反应明显增加·OH的生成并促进癌细胞凋亡。这种级联超分子纳米平台提供了一种有前途的协同放大 CDT 的治疗策略。

Chemodynamic therapy (CDT) has been limited by the tumor microenvironment, such as the low concentration of hydrogen peroxide (H2O2). The combination of therapeutic strategies that increase H2O2 with CDT can synergistically enhance the therapeutic effect. Herein, a novel supramolecular PEG-DNA-ferrocene nanogel that can codeliver glucose oxidase (GOx) and the hypoxia-activable prodrug tirapazamine (TPZ) was developed to synergistically amplify CDT via cascade reactions. The DNA nanogel was size-controllable and DNase I-responsive and exhibited good biocompatibility. Induced by oxygen consumption and H2O2 generation in the catalytic reaction of GOx, the drugs TPZ and ferrocene in the nanogel underwent the hypoxia-based reaction and the Fenton reaction, respectively. The vitro model tests, intracellular ROS test, MTT experiments, and DNA damage assay demonstrated that the H2O2-based cascade Fenton reaction and the hypoxia-based cascade reaction obviously increased ·OH generation and promoted the apoptosis of cancer cells. This cascade supramolecular nanoplatform provided a promising therapeutic strategy to synergistically amplify CDT.