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 targeting products and cause undesired side-reactions. Single-atom catalysts (SACs) with high atomic utilization, identical active site compositions 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, the 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 for preferentially activating specific catalytic process within tumor, functioning as promising candidates for cancer therapy.