Engineering high-performance chemiluminescent probes via enzymatic pocket targeting: high-throughput screening for ultralong afterglow imaging of orthotopic hepatocellular carcinoma

IF 10.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Science China Chemistry Pub Date : 2025-01-02 DOI:10.1007/s11426-024-2296-6

Shuai Huang, Shuaige Bai, Ting Luo, Bin Feng, Min Liu, Fan Zheng, Shuang Huang, Yanpeng Fang, Dan Ding, Wenbin Zeng

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive liver malignancy and the main form of liver cancer. Early diagnosis and treatment of HCC can effectively reduce mortality. Carboxylesterase (CE)-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC. However, traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio. Here, we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques. The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site. Here, CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit (2.5 × 10⁻⁴ U mL⁻¹) and fast recognition ability. CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging (over 12 h) of hepatocellular carcinoma. This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.

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酶袋靶向工程高效化学发光探针：原位肝癌超长余辉成像的高通量筛选

肝细胞癌（HCC）是一种高度侵袭性的肝脏恶性肿瘤，是肝癌的主要形式。早期诊断和治疗可有效降低HCC的死亡率。羧酸酯酶（CE）特异性检测和成像可用于HCC的早期诊断和图像引导手术。然而，传统的光学探针存在选择性差、成像信噪比低的问题。在此，我们构建了一系列基于酶的口袋定向立体裁剪技术的化学发光探针，用于检测羧酸酯酶。通过对识别位点进行基于结构的位阻调整，获得了具有不同独特优异性能的探针。由于CE-2极低的检出限（2.5 × 10−4 U mL−1）和快速识别能力，CE-2已成功用于快速羧酸酯酶抑制剂的高通量筛选。CE-3因其对肝癌的超长化学发光成像（超过12小时），已成功应用于原位肝细胞癌的影像引导手术。本研究将促进肝癌CE抑制药物的快速检测和筛选以及肝细胞癌手术导航领域的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science China Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

14.40

自引率

7.30%

发文量

3787

审稿时长

2.2 months

期刊介绍： Science China Chemistry, co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China and published by Science China Press, publishes high-quality original research in both basic and applied chemistry. Indexed by Science Citation Index, it is a premier academic journal in the field. Categories of articles include: Highlights. Brief summaries and scholarly comments on recent research achievements in any field of chemistry. Perspectives. Concise reports on thelatest chemistry trends of interest to scientists worldwide, including discussions of research breakthroughs and interpretations of important science and funding policies. Reviews. In-depth summaries of representative results and achievements of the past 5–10 years in selected topics based on or closely related to the research expertise of the authors, providing a thorough assessment of the significance, current status, and future research directions of the field.