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

作者：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^*

来源：Biomaterials Science, 2022, 10(4): 1083-1089.

DOI：10.1039/d1bm01675j

• INDUCED LIVER-INJURY
• FLUORESCENT-PROBE
• ENDOGENOUS PEROXYNITRITE
• OXIDATIVE STRESS
• REACTIVE OXYGEN
• GENERATION
• MECHANISMS

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.

• 单位
  北京理工大学; 1