Recently, Weili Zhao group has made new progress in the field of small molecule fluorescent probes. The result was published in an international journal (Sensors & Actuators B. Chemical) under the title “Diketopyrrolopyrrole-based sensor for over-expressed peroxynitrite in drug-induced hepatotoxicity via ratiometric fluorescence imaging”.

Early diagnosis and detection of drug-induced liver injury (DILI) is great significance for the effective prevention and treatment of patients with liver injury. Studies indicate that the up-regulation of peroxynitrite (ONOO‒) levels in liver is profoundly involved in acetaminophen (APAP)-induced liver injury. Herein, we constructed diketopyrrolopyrrole (DPP)-based ratiometric fluorescent probes (DPP-DH-P and DPP-DEG-P) for detecting and imaging ONOO‒. Comparing two probes, DPP-DEG-P exhibited higher signal-to-noise ratio (2750-fold) and lower detection limit (3.5 nM) for tracking ONOO‒ in solution. DPP-DH-P possessing better biocompatibility had been successfully applied to monitor the fluctuation of ONOO‒ in LPS/IFN-γ or APAP-treated hepatocytes with a high signal-to-noise ratio (20-fold) by ratiometric imaging. Moreover, the probe was used to evaluate the repair effect of glutathione on DILI. We unexpectedly discovered that DPP-DH-P and DPP-DH targeted lysosomes and mitochondria, respectively. Based on the change of ONOO‒ induced by APAP, we observed that DPP-DH-P and the generated DPP-DH diffused from lysosome into cytoplasm, and DPP-DH did not target mitochondria due to the effect of endogenous ONOO‒, these indirectly reflected the dysfunction of organelles. Observably, this work will accelerate a deeper comprehending for the pathogenesis of DILI, and furnish an effective tool for the diagnosis and treatment of DILI.

Doctoral student Nannan Wang and master student Han Wang of the Key Laboratory of Special Functional Materials are the co-first authors of the paper. This research was financially supported by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation and Key Scientific and Technological Project of Henan Province.