A molecular imaging tool for monitoring carboxylesterase 2 during early diagnosis of liver-related diseases

Early disease diagnosis is crucial for human health and successful therapy. Carboxylesterase 2 (CES2), the main enzyme found in many tumor tissues, is closely associated with many malignant diseases. Therefore, the ability to detect endogenous CES2-associated diseases can be of therapeutic significance. In this study, we designed a novel mitochondria-targeting near-infrared (NIR) chemosensor (YDT) to visualize the endogenous CES2. This is the first study to track CES2 at the mitochondrial level and present the currently most sensitive CES2 detection sensor. With various features including large Stokes shift, quick response time, excellent selectivity, and ultra-high sensitivity, the sensor can overcome numerous limitations faced by traditional CES2 probes. YDT is an "off -on" chemosensor that releases fluorophore YD-1 upon interacting with CES2, emits strong fluorescence at 660 nm. Importantly, YDT can dynamically monitor immediate changes in CES2 level under external stimuli. Moreover, we used YDT to systematically study the CES2 expression in drug-induced liver injury and its remediation model, as well as in an inflammation model. With these outstanding characteristics, YDT is a considerably promising tool for further research on biological processes and for examining the physiological roles of CES2 in living systems.