Design and synthesis of esterase-activated fluorescent probe for diagnosis and surgical guidance of liver cancer.

IF 5.6 1区化学 Q1 CHEMISTRY, ANALYTICAL Talanta Pub Date : 2025-02-01 Epub Date: 2024-11-12 DOI:10.1016/j.talanta.2024.127210

Yaling Su, Zhongsheng Xu, Jiemin Wang, Jing Qian, Cong Liu, Junqi Shi, Wei Liu, Xiaoli An, Wenwu Qin, Yun Liu

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Abstract

Liver cancer seriously threatens the health of human beings. Studies have found that esterase is overexpressed in liver cancer cells. Therefore, esterase can be one of the biomarkers of liver cancer. Previous literature studies have shown that the structures of fluorescent probe detection groups significantly impact the probes themselves and enzyme detection. In this paper, three "off-on" esterase-activated fluorescent probes (RHO-1, RHO-2 and RHO-3) with different length of the carbon chains of the detection groups were designed and synthesized. Density functional theory (DFT) calculation and Michaelis-Menten equations were applied to study the optical properties and affinity with esterase of the probes. Compared with RHO-1 and RHO-2, RHO-3 showed superior optical properties and affinity with esterase. Subsequently, RHO-3 was further used to detect esterase activity in vitro and in vivo. RHO-3 was the first esterase-activated fluorescent probe applied to image-guided diagnosis and surgical resection of liver cancer. It was expected to be a promising molecular imaging diagnostic tool in clinical applications.

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设计和合成酯酶激活的荧光探针，用于肝癌诊断和手术引导。

肝癌严重威胁人类健康。研究发现，酯酶在肝癌细胞中过度表达。因此，酯酶可以作为肝癌的生物标志物之一。以往的文献研究表明，荧光探针检测基团的结构对探针本身和酶的检测有很大影响。本文设计并合成了三种检测基团碳链长度不同的酯酶激活型荧光探针（RHO-1、RHO-2 和 RHO-3）。应用密度泛函理论（DFT）计算和迈克尔斯-门顿方程研究了探针的光学性质和与酯酶的亲和性。与 RHO-1 和 RHO-2 相比，RHO-3 表现出更优越的光学性质和与酯酶的亲和性。随后，RHO-3 被进一步用于体外和体内酯酶活性的检测。RHO-3 是第一个应用于肝癌图像引导诊断和手术切除的酯酶激活型荧光探针。它有望成为临床应用中一种前景广阔的分子成像诊断工具。

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来源期刊

Talanta 化学-分析化学

CiteScore

12.30

自引率

4.90%

发文量

861

审稿时长

29 days

期刊介绍： Talanta provides a forum for the publication of original research papers, short communications, and critical reviews in all branches of pure and applied analytical chemistry. Papers are evaluated based on established guidelines, including the fundamental nature of the study, scientific novelty, substantial improvement or advantage over existing technology or methods, and demonstrated analytical applicability. Original research papers on fundamental studies, and on novel sensor and instrumentation developments, are encouraged. Novel or improved applications in areas such as clinical and biological chemistry, environmental analysis, geochemistry, materials science and engineering, and analytical platforms for omics development are welcome. Analytical performance of methods should be determined, including interference and matrix effects, and methods should be validated by comparison with a standard method, or analysis of a certified reference material. Simple spiking recoveries may not be sufficient. The developed method should especially comprise information on selectivity, sensitivity, detection limits, accuracy, and reliability. However, applying official validation or robustness studies to a routine method or technique does not necessarily constitute novelty. Proper statistical treatment of the data should be provided. Relevant literature should be cited, including related publications by the authors, and authors should discuss how their proposed methodology compares with previously reported methods.