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, PMF3, has been judiciously developed. For the first time, PMF3 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, PMF3 was successfully used to monitor APAP-induced HClO fluctuations in HepG2 cells via a dual-response mode. Finally, we demonstrated the ability of PMF3 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.