Reversible NIR Ratiometric Probe for Monitoring Redox Homeostasis in Lipid Droplets during Ferroptosis-Driven Liver Injury.

Accurate diagnosis and timely treatment of drug-induced liver injury (DILI) are crucial to preventing progression to other liver diseases or failure. Cellular redox balance may be linked to DILI. Hypochlorous acid (HClO) and glutathione (GSH) are key redox pairs reflecting cellular status. Ferroptosis is critical for understanding liver injury mechanisms. Studies show that DILI is associated with lipid droplet (LD) dysfunction. LDs, essential for lipid metabolism and storage, are linked to ferroptosis and fatty liver. Developing fluorescent probes for LD imaging is vital for studying dynamic physiological processes. Currently, no reversible probes exist to monitor the HClO/GSH redox balance, especially in LDs. To address this, we developed the NIR ratio-fluorescent probe PSeZ-ZD to dynamically monitor the HClO/GSH balance in LDs during ferroptosis and DILI. PSeZ-ZD enables NIR ratio imaging, targets LDs, and detects oxidants and antioxidants. It has detection limits of 51.1 nM for HClO and 1.575 μM for GSH. At the cellular level, PSeZ-ZD successfully images HClO fluctuations with excellent reversibility and LD targeting. It also monitors in situ HClO/GSH in APAP- or INH-induced DILI and evaluates NAC, silybin, and their combination. This probe provides a valuable tool for early DILI diagnosis and treatment, offering new insights into ferroptosis in DILI.