The engineering of a series of multienzyme-mimicking covalent organic frameworks (COFs), COF-909-Cu, COF-909-Fe, and COF-909-Ni, as pyroptosis inducers, remodeling the tumor microenvironment to boost cancer immunotherapy, is reported. Mechanistic studies reveal that these COFs can serve as hydrogen peroxide (H₂O₂) homeostasis disruptors to elevate intracellular H₂O₂ levels, and they not only exhibit excellent superoxide dismutase (SOD)-mimicking activity and convert superoxide radicals (O₂^•−) to H₂O₂ to facilitate H₂O₂ generation, but also possess outstanding glutathione peroxidase (GPx)-mimicking activity and deplete glutathione (GSH) to alleviate the scavenging of H₂O₂. Meanwhile, the outstanding photothermal therapy properties of these COFs can accelerate the Fenton-like ionization process to facilitate their chemodynamic therapy efficiency. One member, COF-909-Cu, can robustly induce gasdermin E (GSDME)-dependent pyroptosis and remodel the tumor microenvironment to trigger durable antitumor immunity, thus promoting the response rate of αPD-1 checkpoint blockade and successfully restraining tumor metastasis and recurrence.

中文翻译：

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工程多酶模拟共价有机框架作为焦亡诱导剂以增强抗肿瘤免疫力

报道了一系列多酶模拟共价有机框架 (COF) 的工程设计，即 COF-909-Cu、COF-909-Fe 和 COF-909-Ni，作为焦亡诱导剂，重塑肿瘤微环境以促进癌症免疫治疗. 机理研究表明，这些 COF 可以作为过氧化氢 (H ₂ O ₂ ) 稳态破坏剂来提高细胞内 H ₂ O ₂水平，它们不仅表现出出色的超氧化物歧化酶 (SOD) 模拟活性和转化超氧自由基 (O ₂ ^{• -} ) 到 H ₂ O ₂以促进 H ₂ O ₂生成，还具有出色的谷胱甘肽过氧化物酶（GPx）模拟活性和消耗谷胱甘肽（GSH）以减轻H ₂ O ₂的清除。同时，这些COFs出色的光热治疗特性可以加速类芬顿电离过程，从而提高其化学动力学治疗效率。其中一个成员，COF-909-Cu，可以强烈诱导gasdermin E (GSDME)依赖性细胞焦亡，重塑肿瘤微环境，触发持久的抗肿瘤免疫，从而提高αPD-1检查点阻断的反应率，成功抑制肿瘤转移和复发。