Nanozyme-Driven Ferroptosis-Cuproptosis Interplay in Lung Cancer

Lung cancer is uniquely amenable to local administration and is characterized by sustained exposure to an oxygen-rich exchange environment and marked metabolic heterogeneity. These features make it a distinctive therapeutic setting for nanozyme-mediated induction of ferroptosis and cuproptosis, while simultaneously imposing more stringent requirements on delivery precision and safety control for therapies based on intense oxidative and metal-induced stress. From the organ-specific context of lung cancer, this review focuses on the catalytic design of nanozymes, strategies for localized pulmonary delivery, and the interplay between ferroptosis and cuproptosis, while evaluating their potential applications in metabolic reprogramming, tumor suppression, and immune sensitization. Current evidence suggests that iron- and copper-associated catalysis, multiple enzyme-mimetic activities, and cascade reactions can amplify lipid peroxidation, deplete reductive capacity, and exacerbate mitochondrial proteotoxic stress, thereby enhancing tumor cell killing. In certain systems, these effects are further accompanied by increased immunogenic cell death and activation of antitumor immunity. Nevertheless, the field is constrained less by a shortage of additional nanoplatforms than by the absence of clear and comparable criteria for defining cuproptosis, insufficient evidence supporting lung cancer-directed local delivery, and the lack of biomarker-guided patient stratification and rational combination strategies.