As a typical chemodynamic therapy (CDT), the Fenton reaction holds great promise in cancer therapy for its effective generation of the cytotoxic hydroxyl radical (^.OH) in situ which induces cancer cell apoptosis. However, the tumor microenvironment is insufficient to meet the optimal conditions for Fenton reaction, which greatly reduces the rate of Fenton reaction and the therapeutic effect of CDT, thereby hindering its application in cancer therapy. Herein, a novel biocompatible nanogel comprised of ferroferric oxide modified β‐cyclodextrin (Fe₃O₄@β‐CD), glucose oxidase (GO_X), and ferrocene (Fc) was fabricated using the host‐guest self‐assembly method for synergistic tumor therapy (Fe₃O₄−GO_X nanogel, FGgel). In the tumor microenvironment, the intratumoral hydrogen peroxide (H₂O₂) could oxidize Fc, leading to the disintegration of the FGgel and the release of GO_X. Subsequently, the released GO_X could catalyze glucose to produce gluconic acid and promote the production of H₂O₂. Meanwhile, in acidic conditions, F₃O₄ served as the Fenton reagent to convert excessive H₂O₂ into highly toxic ^.OH which finally induces tumor cell apoptosis. Extensive in vitro and in vivo studies have confirmed that FGgel can effectively inhibit tumor cell growth with high tumor specificity and good biocompatibility. The excellent anticancer efficiency of FGgel indicates that it is an ideal H₂O₂‐activated nanosystem. As an excellent platform to harness the highly toxic reactive oxygen species in nanomedicine for specific cancer therapy, this strategy may open new doors for further development of progressive therapeutic systems.

中文翻译：

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H2O2响应纳米凝胶，用于增强化学动力学治疗

作为一个典型的chemodynamic疗法（CDT），芬顿反应保持用于其有效产生细胞毒性的羟自由基在癌症治疗中很大的希望（^。原位诱导癌细胞凋亡OH）。然而，肿瘤的微环境不足以满足芬顿反应的最佳条件，这大大降低了芬顿反应的速率和CDT的治疗效果，从而阻碍了其在癌症治疗中的应用。在此，使用主体-客体自组装方法制备了一种新型的生物相容性纳米凝胶，该复合物由三氧化二铁修饰的β-环糊精（Fe ₃ O ₄ @β-CD），葡萄糖氧化酶（GO _X）和二茂铁（Fc）组成。肿瘤治疗（Fe ₃ O ₄-GO _X纳米凝胶，FGgel）。在肿瘤微环境中，肿瘤内过氧化氢（H ₂ O ₂）可以氧化Fc，从而导致FGgel分解和GO _X释放。随后，释放的GO _X可以催化葡萄糖产生葡萄糖酸并促进H ₂ O _2的产生。同时，在酸性条件下，F ₃ O ₄用作芬顿试剂，将过量的H ₂ O ₂转化为剧毒^。OH最终诱导肿瘤细胞凋亡。广泛的体内外研究证实，FGgel具有高的肿瘤特异性和良好的生物相容性，可以有效抑制肿瘤细胞的生长。FGgel优异的抗癌功效表明它是理想的H ₂ O ₂活化纳米系统。作为利用纳米药物中剧毒的活性氧物质进行特定癌症治疗的绝佳平台，该策略可能为进一步发展渐进治疗系统打开新的大门。