A unique probe enables labeling cell membrane and Golgi apparatus and tracking peroxynitrite in Golgi oxidative stress and drug-induced liver injury

Drug-induced liver injury (DILI) is a serious public health issue related to oxidative stress. Peroxynitrite (ONOO−) is considered to be a direct biomarker of DILI. Recently, the Golgi apparatus has become a new choice for the research and treatment of DILI. A probe that can target Golgi to detect ONOO− is therefore of great value for the study of DILI. However, no such probe has been reported. Herein, we report a Golgi-targetable fluorescence probe MG-ONOO for ONOO−, which was prepared by linking a sulfanilamide moiety to a conjugated system of coumarin and hemi-cyanine. The probe shows low cytotoxicity, high sensitivity and selectivity, and rapid response for ONOO− with distinct ratiometric fluorescence changes. Unexpectedly, MG-ONOO shows unique targeting properties in living cells. The probe can target and label the cell membrane first (≤ 30 min incubation) and then the Golgi (≥ 60 min incubation), making it capable of detecting ONOO− not only in Golgi but also on cell membranes. Imaging experiments showed that MG-ONOO could be applied to monitor ONOO− under the oxidative stress of Golgi and in DILI (using mice models). Overall, this work provides a new tool for exploring Golgi oxidative stress and evaluating DILI.