Seeding Janus Zn–Fe Diatomic Pairs on a Hollow Nanobox for Potent Catalytic Therapy

Dual atomic nanozymes (DAzymes) are promising for applications in the field of tumor catalytic therapy. Here, integrating with ultrasmall Fe₅C₂ nanoclusters, asymmetric coordination featuring Janus Zn-Fe dual-atom sites with an O₂N₂-Fe-Zn-N₄ moiety embedded in a carbon vacancy-engineered hollow nanobox (Janus ZnFe DAs-Fe₅C₂) was elaborately developed. Theoretical calculation revealed that the synergistic effects of Zn centers acting as both adsorption and active sites, oxygen-heteroatom doping, carbon vacancy, and Fe₅C₂ nanoclusters jointly downshifted the d-band center of Fe 3d orbitals, optimizing the desorption behaviors of intermediates *OH, thereby significantly promoting catalytic activity. Upon 1064 nm laser irradiation, Janus ZnFe DAs-Fe₅C₂ with superior photothermal conversion efficiency (η = 62.5%) showed thermal-augmented catalytic therapy. Fascinatingly, Janus ZnFe DAs-Fe₅C₂ with multienzymatic properties can suppress the expression of glutathione peroxidase 4 and accelerate the accumulation of lipid peroxides, through which ferroptosis is triggered. Overall, tannin-involved asymmetric Janus ZnFe DAs-Fe₅C₂ will inspire more inventions of biodegradable DAzymes for tumor therapy application.