A novel carboxylesterase 2-targeted fluorescent probe with cholic acid as a recognition group for early diagnosis of drug- and environment-related liver diseases.

Autor: Li J; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China., Ma M; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China; School of Pharmacy, Jilin University, Qianjin Street 2699, Changchun 130012, China., Zhang Z; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China., Xu L; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China., Yang B; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China., Diao Q; Liaoning Key Laboratory of Development and Utilization for Natural Products Active Molecules, School of Chemistry and Life Science, Anshan Normal University, Anshan, China., Ma P; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China. Electronic address: mapinyi@jlu.edu.cn., Song D; College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China; Liaoning Key Laboratory of Development and Utilization for Natural Products Active Molecules, School of Chemistry and Life Science, Anshan Normal University, Anshan, China. Electronic address: songdq@jlu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Dec 05; Vol. 480, pp. 135966. Date of Electronic Publication: 2024 Sep 26.
DOI: 10.1016/j.jhazmat.2024.135966
Abstrakt: Due to the detrimental effects of various harmful substances-such as carcinogens, drug toxicity, and environmental pollutants-on the liver, which can trigger or exacerbate conditions like hepatocellular carcinoma (HCC), drug-induced liver injury (DILI), and non-alcoholic fatty liver disease (NAFLD), accurate detection and monitoring of these diseases are crucial for effective treatment. Carboxylesterase 2 (CES2) is primarily found in the liver and, as a potential biomarker, its accurate detection can enhance the early diagnosis and treatment efficacy of liver diseases. Traditional fluorescence probes for CES2 detection suffer from non-specific recognition groups, leading to poor targeting specificity. To address this limitation, we propose a novel CES2-responsive fluorescent probe utilizing cholic acid (CA) as a recognition group. The probe, LAN-CA, was synthesized by esterifying CA with a near-infrared fluorophore, LAN-OH. This novel fluorescent probe leverages the unique affinity of CA for hepatocytes, ensuring that LAN-CA remains and accumulates specifically within the hepatoenteric circulation. In vitro experiments showed that the probe exhibits superior optical performance compared to traditional benzoate-based probe (LAN-PH), with a detection limit of 0.015 μg/mL. Examination of 56 common biological interferents demonstrated that using CA as a recognition group offers high selectivity. Cell experiments confirmed that LAN-CA is an effective tool for monitoring endogenous CES2 in live cells. Comprehensive evaluations of fluorescence imaging in various mouse models of liver diseases, such as HCC, DILI, and NAFLD, demonstrated that LAN-CA provides exceptional imaging accuracy and therapeutic monitoring capabilities. In conclusion, this probe not only can be a promising tool for accurate liver disease diagnosis, but also can provide valuable insights into treatment efficacy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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