Copper homeostasis imbalance and cuproptosis: Emerging targets and strategies for gastrointestinal tumor therapy

Figure 5 Smart nanomedicine strategies for synergistic cuproptosis therapy. Engineered nanocarriers, including metal-organic frameworks, liposomes, and biomimetic platforms, enable tumor-targeted Cu²⁺ delivery and controlled Cu⁺ release in acidic and glutathione-rich tumor microenvironments. Local copper accumulation may promote cuproptosis-related cytotoxicity and synergize with chemodynamic, photothermal, photodynamic, and immune-activating strategies by enhancing mitochondrial damage and oxidative stress. MOF: Metal-organic framework; ECM: Extracellular matrix; GSH: Glutathione; GSSH: Glutathione thiol; GSSG: Glutathione disulfide; CDT: Chemodynamic therapy; PTT: Photothermal therapy; PDT: Photodynamic therapy; NIR: Near-infrared; ICD: Immunogenic cell death; DAMP: Damage-associated molecular pattern; DC: Dendritic cell; HMGB: High mobility group box protein; ATP: Adenosine triphosphate.