Dynamic Oxygen Vacancy Engineering of Single‐Atom Nanozymes for Boosting Oxidase‐Like Activity

Abstract Single‐atom nanozymes (SANs) encounter significant challenges in achieving optimal activity due to the insufficient synergistic modulation of isolated catalytic sites. Herein, a photochemical reduction strategy is presented for simultaneously constructing Pt‐O 6 catalytic centers and oxygen vacancies (OVs) within mesoporous silica‐supported platinum single‐atoms (mSiO 2 ‐PtSANs). The density of OVs can be dynamically regulated by adjusting the UV exposure time. This UV‐mediated dynamic engineering of OVs significantly enhances the oxidase (OXD)‐like activity of mSiO 2 ‐PtSANs, leading to a 34.3‐fold reduction in the Michaelis–Menten constant ( K m ) value and a 62.8‐fold increase in catalytic efficiency ( K cat / K m ). Density functional theory (DFT) calculations demonstrate that OVs promote O 2 activation, facilitate electron transfer, and reduce the energy barrier for ·OH formation. Engineered with abundant OVs, the mSiO 2 ‐PtSANs drive persistent reactive oxygen species (ROS) generation, which can act as an effective strategy to amplify ferroptotic cell death. To further harness this therapeutic synergy, the ferroptosis inducer RSL3 is loaded into the nanoplatform with a drug loading efficiency of 65.8%, yielding the mSiO 2 ‐PtSANs@RSL3 nanocatalytic agent. This integrated system significantly enhances antitumor efficacy through the synergistic combination of chemodynamic therapy (CDT) and ferroptosis induction, as demonstrated in both in vitro and in vivo models. The study establishes a novel paradigm for the atomically precise design of SANs through OVs‐mediated electronic modulation.