Dihydroxanthene-derived fluorescent probe with near-infrared excitation and emission maxima for detecting human carboxylesterase-2 and bioimaging

Abstract

Carboxylesterases in human body play pivotal roles for catalyzing the hydrolysis of endogenous and exogenous substances such as lipids, thioesters and amides. Carboxylesterase-2 (CES2) as a major isoform of carboxylesterases is highly expressed in human digestive tract, and usually serves as an important mediator for pharmacokinetics and pharmacodynamics of ester medications or ester prodrugs. Therefore, developing effective strategies to detect and track CES2 in cells or tissues is of great significance for understanding its physiological and pharmacological effects on various diseases and therapeutic outcomes. In this study, we synthesized a fluorescent probe (CHQ-E) with near-infrared (NIR) excitation and emission maxima based on dihydroxanthene fluorophore for highly selective and sensitive detection of CES2. This probe exhibited rapid response (3 min), excellent sensitivity (detection limit = 0.35 ng/mL) and high binding affinity (Km = 9.4 μM) towards CES2, as well as low cytotoxicity towards living biosamples. Significantly, the maximum fluorescence excitation and emission wavelengths led to excellent optical properties of this probe including less photodamage, few autofluorescence and superior tissue penetration depth (180 µm). Moreover, CHQ-E has been applied to monitoring CES2 activity in drug-induced liver injury and its remediation models. Results of fluorescence imaging in vivo indicate the broad potential of CHQ-E for clinical diagnosis and evaluation of pharmaceuticals.