Cuproptosis: An emerging strategy for nanomaterial for the treatment of cancer

Cuproptosis is a recently identified form of programmed cell death dependent on copper ions. Its mechanism primarily involves the abnormal accumulation of intracellular copper, which directly binds to and disrupts the metabolic function of lipoylated proteins in the tricarboxylic acid cycle, leading to protein aggregation, toxic stress responses, and ultimately cell death. In recent years, it has emerged as a potential direction for cancer therapy. Nanomedicine-based cuproptosis therapy has achieved significant progress, garnering widespread attention and leading to the development of various novel therapeutic strategies. This review systematically elaborates on the concept and mechanism of cuproptosis, nano-delivery systems for copper ions, the interplay between cuproptosis and other cell death pathways, as well as combination therapies involving cuproptosis. Furthermore, it provides an in-depth analysis of the latest research advances in nanomedicine-mediated cuproptosis. Finally, the review outlines future directions and challenges, emphasizing that ongoing research will continue to elucidate the molecular details of cuproptosis and develop precise, efficient cuproptosis-targeted anti-tumor strategies.