Near-infrared fluorescence imaging tool with large Stokes shift for sensitively detecting carboxylesterase 2 and monitoring its expression in non-alcoholic fatty liver disease

Zhimin Zhang; Jingkang Li; Mo Ma; Hui Shi; Meijun Lu; Fanghui Liang; Xinghua Wang; Pinyi Ma; Yuan Tian; Daqian Song; Ziwei Zhang

doi:10.1016/j.talanta.2024.127378

Near-infrared fluorescence imaging tool with large Stokes shift for sensitively detecting carboxylesterase 2 and monitoring its expression in non-alcoholic fatty liver disease

Talanta. 2024 Dec 14:285:127378. doi: 10.1016/j.talanta.2024.127378. Online ahead of print.

Authors

Zhimin Zhang¹, Jingkang Li², Mo Ma³, Hui Shi², Meijun Lu², Fanghui Liang⁴, Xinghua Wang², Pinyi Ma², Yuan Tian², Daqian Song², Ziwei Zhang⁵

Affiliations

¹ College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, 130012, China; Department of Pharmacy, Changchun Medical College, Changchun, 130031, China.
² College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun, 130012, China.
³ 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.
⁴ Department of Pharmacy, Changchun Medical College, Changchun, 130031, China.
⁵ 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: zzw@jlu.edu.cn.

PMID: 39689640
DOI: 10.1016/j.talanta.2024.127378

Abstract

Non-alcoholic fatty liver disease (NAFLD) now affects more than one quarter of the global population and becomes a heavy public health burden. However, the underlying mechanism for the pathogenesis of NAFLD is still not clear. Carboxylesterase 2 (CES2), highly abundant in the liver and intestine, plays an important role in endogenous lipid metabolism and lipolysis. So far, the literatures for the role of CES2 in the development of NAFLD are still limited. In this study, we designed and synthesized a near-infrared fluorescent probe (HP-LZ-CES2) which can be specifically recognized and hydrolyzed by CES2, releasing a benzoate residue and a fluorophore (HP-LZ) with good fluorescence signal. With this probe, CES2 levels can be quantitatively measured in vitro and qualitatively visualized in living cells and mice. The probe has the advantages of large Stokes shift, high detection sensitivity and good selectivity. Further, the CES2 expression levels were visually investigated in both high-fat cells as the in vitro model for NAFLD and high-fat diet fed mouse as the in vivo model for NAFLD. The cell imaging experiments indicated a reduction of fluorescence signal in high-fat hepatic cells. The in vivo experiments showed an obvious reduction of fluorescence in the liver of NAFLD mouse model, which is consistent with the hepatic cell experiments. In contrast, an enhancement of fluorescence was observed in the intestine of NAFLD mouse model. As a result, the NAFLD mouse model can be visually distinguished from the normal chow mouse by vision. Therefore, the proposed probe can be an auxiliary tool for the diagnosis of NAFLD and a visual tool for understanding CES2's role in the development of NAFLD.

Keywords: Carboxylesterase 2; Cell imaging; In vivo imaging; Near-infrared fluorescent probe; Non-alcoholic fatty liver disease.