A near-infrared AND logic fluorescent probe that simultaneously responds to Cu2+ and hypochlorous acid for the imaging of Wilson's disease.

Wilson's disease (WD) features aberrant hepatic copper accumulation with oxidative and inflammatory injury. Single-target probes responsive to Cu2+ or reactive oxygen species alone have limited specificity for WD imaging in complex biological environments. Here, we report a near-infrared AND logic fluorescent probe, namely DHU-LP, for the simultaneous detection of Cu2+ and hypochlorous acid (HOCl) to enable specific WD imaging. DHU-LP, constructed by integrating an Oxazine 1 fluorophore with a bis(pyridin-2-ylmethyl)amine Cu2+-binding unit, exhibited a pronounced turn-on response at 669 nm only when both Cu2+ and HOCl were present, but showed negligible fluorescence in the presence of either analyte alone. Mechanistic studies confirmed that Cu2+ coordination promoted HOCl-triggered probe activation. DHU-LP displayed good sensitivity and selectivity for the Cu2+/HOCl combination, low cytotoxicity, and favorable liver-targeting capability. In cellular imaging, the probe differentiated WD patient-derived fibroblasts from normal ones under conditions via combined Cu2+/HOCl stimulation signal. In vivo imaging further showed a marked fluorescence response in the liver of WD mice, whereas negligible signal was observed in wild-type mice. This work provides a dual-analyte fluorescent probe for WD-related imaging and highlights the utility of AND logic design for improving imaging specificity in metal-overload-associated disease models.