ABSTRACT Wearable biosensors leverage nanozymes as stable, cost‐effective alternatives to natural enzymes for continuous health monitoring, yet their nonspecific multi‐enzyme activity often causes false‐positive signals, compromising diagnostic accuracy. To address this, we develop a covalent organic framework nanozyme FeSx@COF, with switchable functions triggered by light irradiation, for tracking antibiotic residues in tears. FeSx@COF initially exhibits specific peroxidase (POD)‐like activity, and switches to oxidase (OXD)‐like behavior under light irradiation. Concurrently, ultrasmall FeSx clusters significantly boost the dual‐enzyme capabilities of the pristine COF. Notably, the resulting OXD activity exhibits superior affinity (0.282 m m ) for 3,3',5,5'‐tetramethylbenzidine (TMB) compared to existing photo‐responsive nanozymes. Systematic mechanistic investigation demonstrates that bandgap engineering through ultrasmall FeSx incorporation significantly improves charge carrier separation. Further, the catalytic process is dominated by axial coordination in OXD reaction, with kinetic studies identifying oxygen protonation as the key rate‐limiting step for the O 2 activation pathway. With high accuracy ( R 2 = 0.995 vs. ELISA) and clinical relevance, FeSx@COF is successfully integrated into wearable patches for noninvasive tear monitoring, demonstrating excellent storage stability (>15 days), in vivo biocompatibility, and continuous readout capability. This work pioneers a spatiotemporally precise nanozyme platform for personalized drug adherence tracking, advancing wearable diagnostics.
Wang et al. (Thu,) studied this question.
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