FIGURE 1 Cuproptosis pathway. The copper ions released by the copper ionophore bind to DLAT, causing lipoacylated DLAT oligomerization and Fe-S cluster protein instability, which ultimately triggers cuproptosis.
However, cuproptosis still face several challenges before realizing effective cancer treatment, such as selectively increasing the concentration of copper ions in cancer cells, avoiding copper ion damage to normal cells, and prolonging the time of cuproptosis.30-32 Nanotechnology may provide an alternative to deal with such a dilemma. The past few decades have witnessed the rapid development of nanotechnology, especially in nano-drug delivery, including improved drug solubility, prolonged circulation time, preferential accumulation of drug at lesion area and reduced systemic side effects.33-35 Copper-based nanomaterials represent a novel class of cuproptosis inducers, which can achieve active targeting by surface modifications and passively accumulate to tumor site via enhanced permeability and retention (EPR) effect.36,37 The excessive copper ion binding to DLAT in tumor cells causes aggregation of lipoacylated DLAT, and induces destabilization of Fe-S cluster proteins, which ultimately leads to cuproptosis of tumor cells, thus exert therapeutic effect. Although many reviews elaborate the close relationship between cuproptosis mechanism and cancer, the recent progress in the field of cuproptosis nanomedicine for cancer therapy has not yet been presented.
In this minireview, we first comprehensively elaborated the regulatory mechanism of cuproptosis in the introduction section, and then summarized the representative research on the use of different nanosystem to treat cancer based on the cuproptosis mechanism (Figure 2 ). Finally, the challenges and future research directions were discussed.