Rational Design of an Intramolecular Hydrogen Bond Enhanced Fluorescent Probe for Diagnosis of Drug-Induced Liver Injury

Drug toxicity and related drug-induced liver injury (DILI) have become major biosafety issues. Enzyme-activated fluorescent probes have been demonstrated as a powerful tool for the diagnosis of DILI; however, they suffer from diffusive signal dilution and interference with other organs, thus leading to misassessment of drug toxicity and inaccurate diagnosis. Alkaline phosphatase (ALP) is an important biomarker, and alterations in the enzyme level are tightly correlated to the severity of liver damage. Herein, an enzyme-activated intramolecular hydrogen bond (IMHB) enhanced probe (TPEG-P) was developed for ALP detection in cells and mice models of DILI. Differing from previously reported intermolecular charge transfer (ICT) or the excited-state intramolecular proton transfer (ESIPT) mechanisms, the TPEG-P enables precise recognition and imaging of ALP only through the activation of intramolecular hydrogen bonds and could in situ sensitively detect varying degrees of liver injury caused by drug toxicity. This IMHB strategy will advance the development of enzyme-activated probes and precise bioimaging in the future.