Embedding Atomically Dispersed Manganese/Gadolinium Dual Sites in Oxygen Vacancy‐Enriched Biodegradable Bimetallic Silicate Nanoplatform for Potentiating Catalytic Therapy

Abstract Due to their atomically dispersed active centers, single‐atom nanozymes (SAzymes) have unparalleled advantages in cancer catalytic therapy. Here, loaded with chlorin e6 (Ce6), a hydrothermally mass‐produced bimetallic silicate‐based nanoplatforms with atomically dispersed manganese/gadolinium (Mn/Gd) dual sites and oxygen vacancies (OVs) (PMn SA GMSNs‐V@Ce6) is constructed for tumor glutathione (GSH)‐triggered chemodynamic therapy (CDT) and O 2 ‐alleviated photodynamic therapy. The band gaps of silica are significantly reduced from 2.78 to 1.88 eV by doping with metal ions, which enables it to be excited by a 650 nm laser to produce electron‐hole pairs, thereby facilitating the generation of reactive oxygen species. The Gd sites can modulate the local electrons of the atom‐catalyzed Mn sites, which contribute to the generation of superoxide and hydroxyl radicals ( • OH). Tumor GSH‐triggered Mn 2+ release can convert endogenous H 2 O 2 to • OH and realize GSH‐depletion‐enhanced CDT. Significantly, the hydrothermally generated OVs can not only capture Mn and Gd atoms to form atomic sites but also can elongate and weaken the O‐O bonds of H 2 O 2 , thereby improving the efficacy of Fenton reactions. The degraded Mn 2+ /Gd 3+ ions can be used as tumor‐specific magnetic resonance imaging contrast agents. All the experimental results demonstrate the great potential of PMn SA GMSNs‐V@Ce6 as cancer theranostic agent.