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

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.