Single-Atom Ce-Doped Metal Hydrides with High Phosphatase-like Activity Amplify Oxidative Stress-Induced Tumor Apoptosis

Phosphates within tumors function as key biomolecules, playing a significant role in sustaining the viability of tumors. To disturb the homeostasis of cancer cells, regulating phosphate within the organism proves to be an effective strategy. Herein, we report single-atom Ce-doped Pt hydrides (Ce/Pt–H) with high phosphatase-like activity for phosphate hydrolysis. The resultant Ce/Pt–H exhibits a 26.90- and 6.25-fold increase in phosphatase-like activity in comparison to Ce/Pt and Pt–H, respectively. Mechanism investigations elucidate that the Ce Lewis acid site facilitates the coordination with phosphate groups, while the surface hydrides enhance the electron density of Pt for promoting catalytic ability in H2O cleavage and subsequent nucleophilic attack of hydroxyl groups. Finally, by leveraging its phosphatase-like activity, Ce/Pt–H can effectively regulate intracellular phosphates to disrupt redox homeostasis and amplify oxidative stress within cancer cells, ultimately leading to tumor apoptosis. This work provides fresh insights into noble-metal-based phosphatase mimics for inducing tumor apoptosis.