Copper-coordinated Covalent Organic Framework Produced A Robust Fenton-like Effect Inducing Immunogenic Cell Death of Tumors.

Increasing infiltration of CD8 + T cells can enhance the response rate to immune checkpoint blockade (ICB) therapies. In contrast, immunogenic cell death (ICD) induced by intracellular reactive oxygen species (ROS) is an effective strategy to increase CD8 + T cell infiltration. Cuproptosis was newly defined and reported by Tsvetkov et al. We prepare Cu-coordinated covalent organic framework (COF) in which two valence states of copper ions were simultaneously loaded. On the one hand, Cu 2+ undergoes a valence shift generating Cu + which acts as an effective Fenton-like reagent to catalyze the production of ·OH and 1 O 2 from cellular overexpressed H 2 O 2 , causing DNA damage and lipid peroxidation (LPO), which directly produce cytotoxicity. On the other hand, residual Cu 2+ can effectively deplete endogenous cellular glutathione (GSH), converting it into glutathione disulfide (GSSG), further increasing intracellular oxidative stress and reducing the scavenging of ROS, thus further enhancing the Fenton-like effect and bringing toxic effects on tumor cells. The synergy of these two functions achieves immunogenic cell death, helping for transforming "cold tumor" to "hot tumor" and efficient anti-tumor effects eventually. This work provides new insights into coordinated COF and inspire the development of more versatile COF for biomedical applications. This article is protected by copyright. All rights reserved.