Screening and optimization of a water-soluble near-infrared fluorescent probe for drug-induced liver injury monitoring

Abstract

Peroxynitrite (ONOO^-) is a potential biomarker of drug-induced liver injury (DILI) and is involved in the process of DILI. Therefore, developing a reliable detection method for ONOO^- will greatly contribute to ensuring drug safety and improving treatment efficiency. Here, based on the previous work, two kinds of NIR fluorescence probes PN and SPN were developed with phenyl-hydrazine as the ONOO^- recognition group, which based on two fluorophores RN and SRN that are stable to ONOO^-. A sensitive NIR probe SPN with good water solubility, low detection limit and good biocompatibility was selected through in vitro spectral property screening. Further experimental results show that there is a good linear relationship between the response intensity of probe SPN to ONOO^- and the concentration of ONOO^-, and the detection limit can reach 19.7 nM. At the cellular level, probe SPN can achieve a good and specific response to endogenous and exogenous ONOO^-. Also, the probe SPN can be used for imaging and detection of DILI in zebrafish level and small animal level, indicating that probe SPN can be used as a powerful tool for diagnosis of DILI and efficacy evaluation of therapeutic drugs.

Keywords: Drug-induced liver injury; Fluorescent probe; Near-infrared; Peroxynitrite; Water-soluble.