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.