A novel hepatocyte-targeting ratiometric fluorescent probe for imaging hydrogen peroxide in zebrafish

Abstract

Hydrogen peroxide (H2O2), as one of important reactive oxygen species (ROS), can be endogenously produced in the liver, and used as a biomarker for predicting drug-induced liver injury (DILI). So, it is important to construct an efficient method for monitoring H2O2 in the liver to assess DILI. Herein, a hepatocyte-targeted fluorescent probe (GCP) for ratiometric detection of H2O2 is developed. GCP consists of two main parts: coumarin-pyran-based fluorophore and galactose-based hepatocyte-targetable group. The probe itself shows near-infrared (NIR) emission owing to its extended π-conjugation. Meanwhile, a large emission shift from 706 to 482 nm (224 nm) is observed after the reaction with H2O2. Taking advantage of the spectroscopic property, GCP exhibits high sensitivity toward H2O2 with 19-fold fluorescence ratio enhancement and is highly selective over other ROS. Moreover, the probe possesses a good hepatocyte-targeting ability and is applied for ratiometric monitoring endogenous H2O2 in HepG2 cells. Furthermore, the probe can trace H2O2 level during DILI in HepG2 cells. Most importantly, GCP can locate in the liver of zebrafish and detect H2O2 level in the liver during DILI, which will be a potentially useful tool to assess DILI.