Multifaceted Carbonized Metal–Organic Frameworks Synergize with Immune Checkpoint Inhibitors for Precision and Augmented Cuproptosis Cancer Therapy
Chen Zhao, Xiaoying Tang, Xiaoyuan Chen, Zhenqi Jiang
Abstract
The discovery of cuproptosis, a copper-dependent mechanism of programmed cell death, has provided a way for cancer treatment. However, cuproptosis has inherent limitations, including potential cellular harm, the lack of targeting, and insufficient efficacy as a standalone treatment. Therefore, exogenously controlled combination treatments have emerged as key strategies for cuproptosis-based oncotherapy. In this study, a Cu 2– x Se@cMOF nanoplatform was constructed for combined sonodynamic/cuproptosis/gas therapy. This platform enabled precise cancer cotreatment, with external control allowing the selective induction of cuproptosis in cancer cells. This approach effectively prevented cancer metastasis and recurrence. Furthermore, Cu 2– x Se@cMOF was combined with the antiprogrammed cell death protein ligand-1 antibody (aPD-L1), and this combination maximized the advantages of cuproptosis and immune checkpoint therapy. Additionally, under ultrasound irradiation, the H 2 Se gas generated from Cu 2– x Se@cMOF induced cytotoxicity in cancer cells. Further, it generated reactive oxygen species, which hindered cell survival and proliferation. This study reports an externally controlled system for cuproptosis induction that combines a carbonized metal–organic framework with aPD-L1 to enhance cancer treatment. This precision and reinforced cuproptosis cancer therapy platform could be valuable as an effective therapeutic agent to reduce cancer mortality and morbidity in the future.