Dual-targetable fluorescent probe for mapping the fluctuation of peroxynitrite in drug-induced liver injury model

Abstract

Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions which can cause acute liver failure or even death in severe cases. With the incidence rate increasing over the years, DILI has became a frequent clinical liver disease and a global public health problem. As a biomarker of DILI, the detection of peroxynitrite (ONOO−) has became a powerful tool for the early diagnosis of liver injury. Here, we synthesized five mitochondria-targetable probes, 1–5, for detecting endogenous ONOO−. Through dye-screening, probe 5 was stood out by its excellent performance. In the presence of ONOO−, the fluorescence signal of probe 5 reduced 40-fold in 19 s with a low detection limit (9.36 nM). At the same time, the transformation can be observed with the naked eye under sunlight or UV lamp without being affected by the other reactive species. Even better, with low toxicity and high biocompatibility, probe 5 could successfully detect endogenous ONOO− in the mitochondrion of cells. Finally, probe 5 could specifically target the liver, and can be employed for monitoring the therapeutic effect of hepatoprotective medicine after drug-induced hepatotoxicity in vivo. In brief, probe 5 has the practical application capability for diagnosing the severity of the liver injury and researching the therapeutic effect of antidote in complex bio-systems.