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

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) (PMnSAGMSNs-V@Ce6) is constructed for tumor glutathione (GSH)-triggered chemodynamic therapy (CDT) and O2-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 (center dot OH). Tumor GSH-triggered Mn2+ release can convert endogenous H2O2 to center dot 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 H2O2, thereby improving the efficacy of Fenton reactions. The degraded Mn2+/Gd3+ ions can be used as tumor-specific magnetic resonance imaging contrast agents. All the experimental results demonstrate the great potential of PMnSAGMSNs-V@Ce6 as cancer theranostic agent. A biodegradable single-atom nanozymes with Mn/Gd dual sites embedded in the oxygen vacancy-enriched mesoporous bimetallic silicate nanospheres is massively produced by a facile hydrothermal method. After loading with chlorin e6 and PEGylation, the innovated nanopatform of PMnSAGMSNs-V@Ce6 is used for achieving O2 self-sufficient PDT, tumor GSH-triggered CDT as well as tumor-specific MRI.image