A ratiometric theranostic system for visualization of ONOO⁻ species and reduction of drug-induced hepatotoxicity

Abstract

Peroxynitrite (ONOO^-) is a potent reactive nitrogen species that plays a role as a critical mediator in liver injury elicited by drugs such as acetaminophen (APAP). At a therapeutic dosage, most APAP is metabolized by liver cells and then excreted in the urine. However, excessive APAP intake can cause an acute production of ONOO^-, which induces mitochondrial oxidative stress and necrosis of the liver cells. Therefore, the ONOO^- levels in hepatocytes have been considered as an early sign of hepatotoxicity associated with drug overdosage. Herein, a ratiometric theranostic system based on aggregation-induced emission luminogens (AIEgens) for the visualization of ONOO^- and reduction of drug-induced hepatotoxicity is developed. The AIEgen ATV-PPB shows a ratiometric fluorescence response from red to green upon cleavage of arylboronic ester moieties by ONOO^- with high sensitivity and selectivity. Meanwhile, experiments reveal that ATV-PPB not only acts as a fluorescent probe for ONOO^- but also as an intracellular ONOO^- scavenger to reduce the hepatotoxicity under overdose APAP treatment.