Engineering Dual-Mode-Responsive Probes for Real-Time HClO Monitoring in Drug-Induced Liver Injury

Given the critical role of HClO in drug-induced liver injury (DILI), it is essential to establish an accurate and reliable technique for the in situ monitoring of its dynamic changes. Herein, by integrating a phenothiazinecoumarin and a leucomethylene moiety through an aliphatic diamine, a robust dual-mode-responsive HClO probe, <b>PMF3</b>, has been judiciously developed. For the first time, <b>PMF3</b> can simultaneously respond to HClO through fantastic ratiometric (from 630 to 500 nm) and NIR fluorescence (690 nm) turn-on modes with excellent sensitivity and selectivity, thereby effectively overcoming the limitations of currently reported single-response-mode HClO probes. Encouraged by these impressive sensing properties, <b>PMF3</b> was successfully used to monitor APAP-induced HClO fluctuations in HepG2 cells via a dual-response mode. Finally, we demonstrated the ability of <b>PMF3</b> to monitor HClO fluctuations in the liver of DILI mice, and dual-mode fluorescence imaging of DILI model liver tissue sections was also achieved, highlighting its potential value in elucidating pathological mechanisms and facilitating clinical diagnosis of DILI.