Engineering Multienzyme‐Mimicking Covalent Organic Frameworks as Pyroptosis Inducers for Boosting Antitumor Immunity

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Abstract
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.
Funding Information
  • National Natural Science Foundation of China (82002879)
  • China Postdoctoral Science Foundation (2021M692475, 2021T140524, XJ2021037)
  • National Natural Science Foundation of China (82072996, 81874131)
  • National Natural Science Foundation of China (22025106, 91545205, 91622103, 21971199)
  • National Key Research and Development Program of China (2018YFA0704000)

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