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用于在癌细胞中精确检测SO的生物素引导和线粒体靶向荧光探针的研发。

The development of a biotin-guided and mitochondria-targeting fluorescent probe for detecting SO precisely in cancer cells.

作者信息

Zhang Yunyan, Kong Xiuqi, Li Min, Yin Yaguang, Lin Weiying

机构信息

Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, University of Jinan, Jinan, Shandong, 250022, PR China.

Institute of Fluorescent Probes for Biological Imaging, School of Chemistry and Chemical Engineering, School of Materials Science and Engineering, University of Jinan, Jinan, Shandong, 250022, PR China.

出版信息

Talanta. 2021 Apr 1;225:121992. doi: 10.1016/j.talanta.2020.121992. Epub 2020 Dec 18.

Abstract

Mitochondrial sulfur dioxide (SO) is very closely associated with various activities of cancer cell. However, the specific physiological and pathological roles of mitochondrial SO in cancer cells are still not well defined. Lacking a powerful molecular tool for detecting mitochondrial SO in cancer cells precisely is an essential factor. So it is urgent to develop a specific method for monitoring mitochondrial SO in cancer cells. Herein, we described a distinct cancer cell-specific fluorescent probe NS for detecting mitochondrial SO accurately in cancer cells. Biotin, possessing of high affinity for cancer cells, was decorated into probe to provide its cancer cell-targeting property. Moreover, the positive charge hemicyanine group was used to anchor mitochondria selectively. A series of spectral results from concentration titration, dynamics and selectivity experiments showed that NS had high sensitivity, fast response and high selectivity to SO. These properties render NS ability for detecting SO in living cells. In biological imaging, the achievements in detecting exogenous and endogenous SO displayed the probe had favorable response to SO in living cells with well biocompatibility. Significantly, assisted by competitive experiments with excess biotin, NS demonstrated distinct cancer cell-targeting for detecting mitochondrial SO. Furthermore, NS could locate mitochondria specially and detect mitochondrial SO in cancer cells by co-localization. Moreover, NS can trace SO in zebrafish with long wavelength emission. Therefore, NS can achieve in tracing mitochondrial SO selectively in cancer cells. It would be a powerful tool for well defining the physiological and pathological roles of mitochondrial SO in cancer cells.

摘要

线粒体二氧化硫(SO)与癌细胞的各种活动密切相关。然而,线粒体SO在癌细胞中的具体生理和病理作用仍未明确。缺乏一种能精确检测癌细胞中线粒体SO的强大分子工具是一个关键因素。因此,迫切需要开发一种监测癌细胞中线粒体SO的特异性方法。在此,我们描述了一种独特的癌细胞特异性荧光探针NS,用于在癌细胞中准确检测线粒体SO。对癌细胞具有高亲和力的生物素被修饰到探针中,以赋予其癌细胞靶向特性。此外,带正电荷的半菁基团用于选择性地锚定线粒体。浓度滴定、动力学和选择性实验的一系列光谱结果表明,NS对SO具有高灵敏度、快速响应和高选择性。这些特性使NS具备在活细胞中检测SO的能力。在生物成像中,检测外源性和内源性SO的成果表明该探针在活细胞中对SO具有良好的响应,且生物相容性良好。值得注意的是,在过量生物素的竞争实验辅助下,NS在检测线粒体SO时表现出明显的癌细胞靶向性。此外,NS可以特异性地定位线粒体,并通过共定位检测癌细胞中的线粒体SO。而且,NS可以在斑马鱼中以长波长发射追踪SO。因此,NS能够在癌细胞中选择性地追踪线粒体SO。它将成为明确线粒体SO在癌细胞中的生理和病理作用的有力工具。

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