Dual-ion Triggered Dual Reactive Oxygen Species Modulation Breaks Intrinsic pH Limitations of Nanozymes for Sensitive Lead(ll) Detection

The pH-dependent activity of nanozymes, optimal in acidic conditions but inert at neutral pH, significantly limits their practical applications. Herein, we demonstrate a dual-ion (Pb 2+ /Cl − ) modulation strategy that activates nanozymes at neutral pH through the spatially controlled generation of dual reactive oxygen species (ROS). Using Au@Pt core-shell nanoparticles (with negligible peroxidase (POD)-like activity at pH 7.0) as a model, we elucidate two synergistic pathways: (i) Pb 2+ -driven structural reconstruction to form catalytically active Pb-Au@Pt species, and (ii) Cl − -mediated electronic modulation for dual-ROS (ClO − and 1 O 2 ) generation. This system circumvents proton dependence through an optimized electron transfer in a nanozyme catalysis system. A photothermal biosensing platform leveraging this mechanism demonstrates sensitive Pb 2+ detection (limit of detection: 1.36   nM, S/N = 3) with >100-fold selectivity against interferents. Unlike conventional single-ROS or surface-engineering methods, our ionic strategy introduces three paradigm-shifting advantages: (i) complete decoupling of catalysis from intrinsic material properties, (ii) elimination of the need for nanostructure redesign, and (iii) establishment of a dual-ROS generation framework. This work redefines nanozyme activation mechanisms while providing actionable principles for next-generation biosensor designs, particularly in physiological environments.