Rational design of a near-infrared fluorescent probe for rapid monitoring of carboxylesterase in live cells and drug-induced liver injury mice.

BACKGROUND: Carboxylesterase (CE) is an important enzyme that mainly exists in liver cells and can catalyze the hydrolysis of esters in a variety of pharmaceuticals and xenobiotics. Real-time and non-invasive imaging of CE is of great significance for the study of CE-related metabolic diseases. Although fluorescence sensing technology is considered a promising candidate, the slow response rate (> 60 min), low sensitivity, and short emission wavelength (<650 nm) of most CE probes limit their practical application. Therefore, it is significant and urgent to develop novel fluorescent probes for the rapid diagnosis of CE-related diseases.

RESULTS: Herein, a near-infrared fluorescent probe, CF3-BDP-CE, has been developed by introducing acetyl as the CE recognition unit into the fluorophore meso-trifluoromethyl-BODIP for the detection of CE. CF3-BDP-CE exhibited a remarkable fluorescence enhancement at 690 nm for CE with a limit of detection of 7.9 × 10-4 U/mL. Importantly, the fast response kinetics (within 3 min) make CF3-BDP-CE superior to most reported probes. The emission turn-on mechanism was confirmed by theoretical calculation, revealing that after the hydrolysis of CF3-BDP-CE, the intramolecular charge transfer process leads to strong fluorescence. Furthermore, CF3-BDP-CE has been successfully applied to real-time imaging of endogenous CE changes in living cells and to imaging CE activity differences between tumor and normal cells. In addition, CF3-BDP-CE has been successfully used to track CE abnormalities in acetaminophen-induced liver injury model mice.

SIGNIFICANCE: A NIR fluorescent probe CF3-BDP-CE was developed to effectively track the dynamic change of CE fluctuation in living cells and mice, with potential applications in the diagnosis of CE-related diseases.