Confined synthesis of ternary FeCoMn single-atom nanozyme in N-doped hollow mesoporous carbon nanospheres for synergistic chemotherapy and chemodynamic cancer therapy

Recently, nanozymes show increasing biological applications and promising possibilities for therapeutic intervention, while their mediated therapeutic outcomes are severely compromised due to their insufficient catalytic activity and specificity. Herein, ternary FeCoMn single atoms were incorporated into N-doped hollow mesoporous carbon nanospheres by in situ confinement pyrolysis at 800 °C as high-efficiency nanozyme. The confinement strategy endows the as-prepared nanozyme with the enhanced catalase- and oxidase-like activities. Specifically, the FeCoMn TSAs/N-HCSs nanozyme can decompose intracellular H₂O₂ to generate O₂ and subsequently convert O₂ to cytotoxic superoxide radicals (O₂^∙-), which can initiate cascade enzymatic reactions in tumor microenvironment (TME) for chemodynamic therapy (CDT). Moreover, the cancer therapy was largely enhanced by loading with doxorubicin (DOX). Impressively, the FeCoMn TSAs/N-HCSs nanozyme-mediated CDT and the DOX-induced chemotherapy endow the DOX@FeCoMn TSAs/N-HCSs with effective tumor inhibition, showing the superior therapeutic efficacy.