Coordination Number-Tuned FeNx Single-Atom Nanozymes for Sustained Peroxidase-Like Catalysis in Tumor Therapy.

Abstract

Peroxidase (POD)-like catalysis by single-atom nanozymes (SAEs) under sustained H2O2 exposure requires both rapid substrate activation and durable catalytic turnover, both of which are closely linked to the coordination environment of metal sites. However, how the coordination number governs their balance remains unclear, especially when the interaction strength between SAEs and H2O2 is tuned. Herein, we construct three structurally comparable FeNx-SAEs (x = 4, 3, and 2), revealing a volcano-like relationship between POD-like activity and H2O2 adsorption strength. The selected FeN3-SAE exhibits the highest POD-like activity (1.52 × 10-6 M s-1), which is 1.9- and 4.1-fold greater than those of FeN2-SAE and FeN4-SAE, respectively. Moreover, the FeN3-SAE sustains efficient H2O2 consumption and robust •OH generation during prolonged catalysis, whereas the FeN4-SAE suffers from inadequate H2O2 activation, and the FeN2-SAE undergoes rapid kinetic decay. Combined experiments and theoretical calculations attribute this performance to well-balanced H2O2 adsorption at the FeN3 site, which facilitates substrate activation, intermediate desorption, and active-site regeneration. Both cellular and animal experiments reveal that FeN3-SAE enables continuous H2O2 conversion into cytotoxic •OH, depleting GSH and triggering tumor suppression accompanied by immune activation. This study provides mechanistic insights into sustained POD-like catalysis from the perspective of coordination number-regulated adsorption‒turnover balance.

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