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一种用于体外和体内高灵敏度检测乙酰胆碱酯酶活性的新型开启型近红外荧光探针。

A novel turn-on near-infrared fluorescent probe for highly sensitive in vitro and in vivo detection of acetylcholinesterase activity.

作者信息

Xing Lei, Ma Pinyi, Chen Fangfang

机构信息

Key Laboratory of Pathobiology, Ministry of Education, Nanomedicine and Translational Research Center, China-Japan Union Hospital of Jilin University, Changchun 130030, China.

College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Changchun 130012, China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2024 Apr 5;310:123954. doi: 10.1016/j.saa.2024.123954. Epub 2024 Jan 26.

DOI:10.1016/j.saa.2024.123954
PMID:38290281
Abstract

Acetylcholinesterase (AChE) is a key enzyme in the cholinergic pathway of the nervous systems, with its aberrant expression linked to various diseases. In this study, we have developed a novel Turn-On near-infrared fluorescent probe, TQ-AChE, for the sensitive and selective detection of AChE activity. Characterized by its near-infrared emission at 740 nm, TQ-AChE effectively overcomes the limitations of traditional fluorescent probes, such as short excitation wavelengths and limited tissue penetration, crucial for both in vitro and in vivo applications. The probe's low limit of detection (LOD) of 0.02 U/mL for AChE makes it highly sensitive, enabling rapid quantification of AChE activity in serum effectively. Cell imaging studies demonstrate that TQ-AChE can confirm higher AChE activity expression in normal liver cells compared to liver cancer cells. TQ-AChE can also monitor AChE fluctuations in APAP-induced acute effectively, facilitating the evaluation of the efficacy of liver detoxifying agents. Additionally, in vivo studies in mouse models validate the potential of the probe in real-time monitoring of AChE expression in liver injury. The ability of TQ-AChE to visualize AChE expression signifies its potential as a promising tool for early liver disease diagnosis and therapeutic monitoring, opening new possibilities in hepatological research and clinical diagnostics.

摘要

乙酰胆碱酯酶(AChE)是神经系统胆碱能途径中的一种关键酶,其异常表达与多种疾病相关。在本研究中,我们开发了一种新型的开启型近红外荧光探针TQ - AChE,用于灵敏且选择性地检测AChE活性。TQ - AChE以其在740 nm处的近红外发射为特征,有效克服了传统荧光探针的局限性,如激发波长短和组织穿透性有限等问题,这对于体外和体内应用都至关重要。该探针对AChE的低检测限(LOD)为0.02 U/mL,使其具有高灵敏度,能够有效快速定量血清中的AChE活性。细胞成像研究表明,与肝癌细胞相比,TQ - AChE可以证实正常肝细胞中AChE活性表达更高。TQ - AChE还能有效监测对乙酰氨基酚诱导的急性肝损伤中AChE的波动情况,有助于评估肝脏解毒剂的疗效。此外,在小鼠模型中的体内研究验证了该探针在实时监测肝损伤中AChE表达的潜力。TQ - AChE可视化AChE表达的能力表明其作为早期肝病诊断和治疗监测的有前景工具的潜力,为肝脏学研究和临床诊断开辟了新的可能性。

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Chem Biomed Imaging. 2024 Oct 17;3(5):332-340. doi: 10.1021/cbmi.4c00058. eCollection 2025 May 26.