Recent Progress in Fluorescent Sensors for Drug-Induced Liver Injury Assessment.

Drug-induced liver injury (DILI) is a persistent concern in drug discovery and clinical medicine. The current clinical methods to assay DILI by analyzing the enzymes in serum are still not optimal. Recent studies showed that fluorescent sensors would be efficient tools for detecting the concentration and distribution of DILI indicators with high sensitivity and specificity, in real-time, in situ, and with low damage to biosamples, as well as diagnosing DILI. This review focuses on the assessment of DILI, introduces the current mechanisms of DILI, and summarizes the design strategies of fluorescent sensors for DILI indicators, including ions, small molecules, and related enzymes. Some challenges for developing DILI diagnostic fluorescent sensors are put forward. We believe that these design strategies and challenges to evaluate DILI will inspire chemists and give them opportunities to further develop other fluorescent sensors for accurate diagnoses and therapies for other diseases.

Precise Synthesis of GSH-Specific Fluorescent Probe for Hepatotoxicity Assessment Guided by Theoretical Calculation.

Drug-induced hepatotoxicity is the main cause of acute liver injury, and its early diagnosis is indispensable in pharmacological and pathological studies. As a hepatotoxicity indicator, the GSH distribution in the liver could reflect the damage degree in situ. In this work, we have provided a theoretical design strategy to determine the generation of photo-induced electron transfer mechanism and achieve high selectivity for the target. After that, we precisely synthesized a novel near-infrared fluorescent probe BSR1 to specifically monitor endogenous GSH and hepatotoxicity in biosystem with a moderate fluorescent quantum yield (Φ = 0.394) and low detection limit (83 nM) under this strategy. Moreover, this mapping method for imaging GSH depletion in vivo to assay hepatotoxicity may provide a powerful molecular tool for early diagnosis of some diseases and contribute to assay hepatotoxicity for the development of new drugs. Importantly, this theoretical calculation-guided design strategy may provide an effective way for the precise synthesis of the target-specific fluorescent probe and change this research area from "trial-and-error" to concrete molecular engineering.