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

• Published in: Biomaterials science 2022-02, Vol.1 (4), p.183-189
• Main Authors: Chau, Joe H. C, Zhang, Ruoyao, Lee, Michelle M. S, Lam, Kristy W. K, Yu, Eric Y, Lam, Jacky W. Y, Kwok, Ryan T. K, Tang, Ben Zhong
• Format: Article
• Language: English
• Subjects: Acetaminophen - toxicity; Animals; Chemical and Drug Induced Liver Injury; Fluorescent indicators; Liver; Mice; Mice, Inbred C57BL; Necrosis; Peroxynitrous Acid; Pharmaceutical Preparations; Precision Medicine; Reduction; Selectivity; Visualization
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d1bm01675j

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. A ratiometric theranostic probe, ATV-PPB, is designed to simultaneously visualize and eliminate ONOO − . Red emissive ATV-PPB originally on mitochondria is transformed to green emissive ATV-Py and translocated to lipid droplets after cleavage by ONOO − .