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

Abstract

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.

Dual-channel fluorescent probe for the simultaneous monitoring of peroxynitrite and adenosine-5’-triphosphate in cellular applications

“…ROS and RNS are regarded as biomarkers in DILI, which has been detected by various fluorescent probes. 19,21 Previous studies confirm ATP production is decreased via APAP. 22,[42][43] APAP-induced hepatoxicity was chosen as the model for ATP-LW to investigate whether the two species can be regarded as early diagnostic biomarkers.…”

“…This model was chosen due to the importance of pre-clinical tools for the screening of drug-induced liver injury (DILI) associated with drugs like APAP are crucial for drug development. [19][20][21] Moreover, the model was selected because APAP can result in a depletion of ATP and an increase in the levels of ONOO − (Scheme S1). [22][23] It is important to note, we first disclosed our probe ATP-LW as a ChemRxiv preprint, 24 however, we felt that the paper could be substantially improved with the addition of biological experiments and so submission for publication of that paper was delayed.…”

Rational Modulation Strategies to Improve Bioimaging Applications for Organic NIR‐II Fluorophores

“…Inspired by the pioneering work of Alexander L. Antaris et al, certain building blocks have created NIR-II fluorophores. [17] One of the most common methods include exploiting benzo[1,2-c:4,5-c']bis( [1,2,5]thiadiazole) (BBTD) as an electron acceptor core attached to thiophene, triphenylamine, and their derivatives. In addition, upon binding with the aryl group, the cyano group could induce intermolecular electron transfer to ensure the emission of NIR-II fluorescence.…”

“…Imaging is an indispensable method applied in cancer research, clinical experiments, and medical practice. [1][2][3] Among numerous imaging methods, fluorescence-based imaging methods enable scientists to uniquely visualize and interpret biological events, which act as a direct, easy-operative, and noninvasive approach for studying life sciences. [4][5][6] Conventional fluorescence imaging methods exploit fluorescence in the visible (400-650 nm) and the first near-infrared window (NIR-I) regions (650−950 nm), which exhibit defects of relatively low tissue penetration, unavoidable tissue absorption and scattering, and undesired autofluorescence that deteriorate the imaging efficacy.…”

A ratiometric theranostic system for visualization of ONOO− species and reduction of drug-induced hepatotoxicity

“…Currently, various techniques for ONOO − detection have been reported, including gas chromatography mass spectrometry, 12 liquid chromatography mass spectrometry, 12 electron spin resonance 13 and fluorescence imaging. [14][15][16][17][18][19][20][21][22][23][24] Among them, fluorescence imaging techniques allow real-time monitoring of ONOO − in biomolecules and organelles noninvasively. Notably, the fast response and high-sensitivity properties of fluorescent probes make them highly desirable for detecting those RONS that have very short lifetimes.…”