Cu²⁺ Embedded Three-Dimensional Covalent Organic Framework for Multiple ROS-Based Cancer Immunotherapy

Reactive oxygen species (ROS)-based cancer treatments have attracted much attention in recent years. However, most patients respond poorly to the monotypic ROS during these treatments. In this work, a multiple ROS-based cancer immunotherapy synergistic strategy has been developed to enhance the therapeutic effect of cancer. We prepare a three-dimensional covalent organic framework (3D COF-TATB), and embed copper ions (Cu²⁺) into the skeleton to obtain multifunctional nanomaterial, 3D Cu@COF-TATB. In this system, porphyrins in 3D COF-TATB serve not only as the photosensitizer for photodynamic process to produce singlet oxygen(¹O₂), but also as the binding sites to complex with Cu²⁺. Cu²⁺ can be reduced by the GSH to generate Cu⁺ to produce hydroxyl radical (•OH) through the Fenton-like reaction. Moreover, the generated multiple types of ROS induce the immunogenic cell death (ICD) of cancer cells to improve the immunogenicity and further activate an immune response for attacking the tumor. Combining with the immunoblocking inhibitor (aPD-1), 3D Cu@COF-TATB can effectively inhibit the tumor growth. This work will provide a guidance for multimodal cancer therapy in future clinical treatment settings.