Disulfidptosis and Enzymatic‐Therapy Augmented Cuproptosis via Adding Spear and Discarding Shield Strategy

O-induced self-cascade enzymatic reactions (OXD, SOD, and POD) are first achieved, which lead to significant mitochondrial dysfunction. Benefiting from the dual inhibition of mitochondrial metabolism and GOx-induced glycolysis, the provision of ATP is fundamentally blocked, thereby further downregulating the ATPase to prevent the efflux of copper ions. Collectively, the "adding spear and discarding shield" strategy dramatically inhibits primary tumor growth in vivo (73.5%). This work first demonstrates disulfidptosis-augmented cuproptosis, and will also provide unique inspiration for regulating both the positive and negative directions in cuproptosis.