Cuproptosis: an emerging domain for copper-based nanomaterials mediated cancer therapy

Cuproptosis, a newly discovered copper-dependent mode of cell death, has received extensive attention in the field of cancer therapy due to its specific activation pathway. Rapid accumulation of large amounts of copper ions within the cancer cells to achieve copper overload is the key to activating cuproptosis. Advanced nanotechnology offers considerable promise for delivering ions to cancer cells, in which copper-based nanomaterials have been proposed to evoke cuproptosis-mediated cancer therapy. However, it is still a great challenge to induce copper overload specifically in tumors and efficiently activate subsequent cuproptosis-related molecular pathways. Therefore, it is necessary to summarize the strategies used to effectively activate or amplify cuproptosis based on currently developed copper-based nanomaterials, providing ideas for the design of nanomaterials in the future. In this review, copper-based nanomaterials that can be used to activate cuproptosis are systematically classified for nanomaterials selection. Subsequently, cuproptosis sensitization strategies using copper-based nanomaterials are provided to amplify the therapeutic efficiency. Meanwhile, cuproptosis-related combination therapies for maximizing treatment efficacy are delineated. Ultimately, the remaining challenges and feasible future directions in the use of cuproptosis for tumor therapy based on copper-based nanomaterials are also discussed.