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.