Synthesis of a Turn-On Isophorone-Based Near-Infrared Fluorescent Probe for Specific Recognition of Carboxylesterase 2 and Bioimaging

Carboxylesterase 2 (CES2) plays critical roles in lipid metabolism and exogenous detoxification, yet current detection methods lack specificity in complex biological systems. To overcome this limitation, we developed CLC-CES2, a near-infrared fluorescent probe rationally designed based on CES2's substrate recognition mechanisms. This probe demonstrates exceptional performance with near-infrared emission (695 nm), a large Stokes shift (145 nm), and a low detection limit (0.021 μg/mL). Biological validation using live cell imaging and zebrafish models demonstrated successful detection of endogenous CES2 activity. These results establish CLC-CES2 as an efficient molecular tool for investigating CES2- associated physiological and pathological processes.