Targeted ZnO@CuEA Nanoplatform for Cuproptosis‐Based Synergistic Cancer Therapy

ABSTRACT Gastric cancer is a common malignant tumour. Copper‐induced cell death, a recently discovered form of metal ion‐related cell death, has garnered significant attention from researchers. We synthesised a multifunctional nanoparticle, ZnO@CuEA, and characterised its morphology using transmission electron microscopy. Cytotoxicity was analysed via CCK8 assays and calcein‐AM staining. The tumour‐targeting capability of ZnO@CuEA was validated using confocal microscopy and in vivo imaging experiments. RNA‐seq and proteomic analysis were conducted to assess changes in mRNA and protein expression before and after ZnO@CuEA treatment. Lysosomal β‐galactosidase staining was employed for cellular senescence detection, and protein expression levels were analysed via Western blot. Finally, in vivo experiments demonstrated the tumour‐inhibitory effect of ZnO@CuEA. ZnO@CuEA is a multifunctional nanoparticle capable of targeting tumour cells and inducing cuproptosis. In vivo experiments showed that ZnO@CuEA exhibits significant antitumor activity. The multifunctional nanoparticles synthesised in this study provide a novel therapeutic approach for cancer treatment.