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一种用于高尔基体中谷胱甘肽的比率检测的荧光探针及其在活性细胞器靶向治疗中的应用。

An Integrated Fluorescent Probe for Ratiometric Detection of Glutathione in the Golgi Apparatus and Activated Organelle-Targeted Therapy.

机构信息

School of Water Conservancy and Environment, University of Jinan, Jinan 250022, China.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

出版信息

Anal Chem. 2021 Dec 7;93(48):16105-16112. doi: 10.1021/acs.analchem.1c03836. Epub 2021 Nov 19.

DOI:10.1021/acs.analchem.1c03836
PMID:34797641
Abstract

Cancer is a serious threat to human health, and there is an urgent need to develop new treatment methods to overcome it. Organelle targeting therapy, as a highly effective and less toxic side effect treatment strategy, has great research significance and development prospects. Being an essential organelle, the Golgi apparatus plays a particularly major role in the growth of cancer cells. Acting as an indispensable and highly expressed antioxidant in cancer cells, glutathione (GSH) also contributes greatly during the Golgi oxidative stress. Therefore, it counts for much to track the changes of GSH concentration in Golgi for monitoring the occurrence and development of tumor cells, and exploring Golgi-targeted therapy is also extremely important for effective treatment of cancer. In this work, we designed and synthesized a simple Golgi-targeting fluorescent probe for accurately detecting GSH. The probe reacting with GSH decomposes toxic substances to Golgi, thereby killing cancer cells. At the same time, the ratiometric fluorescent probe can detect the concentration changes of GSH in Golgi stress with high sensitivity and selectivity in living cells. Therefore, such a GSH-responsive fluorescent probe with a Golgi-targeted therapy effect gives a new method for accurate treatment of cancer.

摘要

癌症是对人类健康的严重威胁,因此迫切需要开发新的治疗方法来克服它。细胞器靶向治疗作为一种高效且毒副作用较小的治疗策略,具有重要的研究意义和发展前景。高尔基体作为一种必需的细胞器,在癌细胞的生长中起着特别重要的作用。谷胱甘肽(GSH)作为癌细胞中不可或缺且高度表达的抗氧化剂,在高尔基体氧化应激中也有很大的贡献。因此,跟踪高尔基体中 GSH 浓度的变化对于监测肿瘤细胞的发生和发展非常重要,探索高尔基体靶向治疗对于有效治疗癌症也非常重要。在这项工作中,我们设计并合成了一种简单的高尔基体靶向荧光探针 ,用于准确检测 GSH。探针 与 GSH 反应后会分解有毒物质到高尔基体,从而杀死癌细胞。同时,该比率型荧光探针可以在活细胞中高灵敏度和选择性地检测高尔基体应激中 GSH 的浓度变化。因此,这种具有高尔基体靶向治疗效果的 GSH 响应荧光探针为癌症的精确治疗提供了一种新方法。

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