Theoretical calculation-guided engineering of Fe-Mn based dual-center single-atom catalysts for synergistic tumor therapy

Tumor therapy employing metal-based nanomaterials to convert the abundant H₂O₂ in tumor microenvironment (TME) to oxygen (O₂) and hydroxy radical (·OH) has attracted substantial attention. However, the generally complex structure of metal nanosystems may have poor catalytic selectivity towards the target and hence cause undesired side reactions. Single-atom catalysts (SACs) with high atomic utilization, composition of identical active site and tunable reaction pathway can be harnessed to realize the well-controlled and highly-selective conversion of H₂O₂ for cancer therapy. Herein, a series of dual single-atom catalysts (DSACs) containing two metal centers (Fe-Se₆, Mn-Se₆) are proposed. As guided by theoretical calculations, DSACs with equal proportions of Fe and Mn (termed as Fe/Mn@PSe₃) exhibit the optimal reaction barriers towards the production of both ·OH and O₂ by catalyzing H₂O₂. In response to the elevated TME H₂O₂, Fe/Mn@PSe₃ can produce ·OH to trigger chemodynamic therapy (CDT), and boost O₂ generation to alleviate tumor hypoxia and its mediated immunosuppression. In addition, its mild hyperthermia feature enhances the anti-tumor effects of CDT and immune therapy, causing an efficient synergistic tumor suppression outcome. The study provides new insights into highly selective nanomaterial design that preferentially activating specific catalytic processes within tumor, functioning as promising candidates for cancer therapy.