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一种新型 HOCl-激活型荧光探针及其在水环境和生物体系中的应用。

A new-type HOCl-activatable fluorescent probe and its applications in water environment and biosystems.

机构信息

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

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

出版信息

Sci Total Environ. 2022 Sep 15;839:156164. doi: 10.1016/j.scitotenv.2022.156164. Epub 2022 May 21.

Abstract

The outbreak and spread of Corona Virus Disease 2019 (COVID-19) has led to a significant increase in the consumption of sodium hypochlorite (NaOCl) disinfectants. NaOCl hydrolyzes to produce hypochlorous acid (HOCl) to kill viruses, which is a relatively efficient chlorine-based disinfectant commonly used in public disinfection. While people enjoy the convenience of NaOCl disinfection, excessive and indiscriminate use of it will affect the water environment and threaten human health. Importantly, HOCl is an indispensable reactive oxygen species (ROS) in human body. Whether its concentration is normal or not is closely related to human health. Excessive production of HOCl in the body contributes to some inflammatory diseases and even cancer. Also, we noticed that the concentration of ROS in cancer cells is about 10 times higher than that in normal cells. Herein, we developed a HOCl-activatable biotinylated dual-function fluorescent probe BTH. For this probe, we introduced biotin on the naphthalimide fluorophore, which increased the water solubility and enabled the probe to aggregate in cancer cells by targeting specific receptor overexpressed on the surface of cancer cell membrane. After reacting to HOCl, the p-aminophenylether moiety of this probe was oxidatively removed and the fluorescence of the probe was recovered. As expected, in the PBS solution with pH of 7.4, BTH could give full play to the performance of detecting HOCl, and it has made achievements in detecting the concentration of HOCl in actual water samples. Besides that, BTH had effectively distinguished between cancer cells and normal cells through a dual-function discrimination strategy, which used biotin to enrich the probe in cancer cells and reacted with overexpressed HOCl in cancer cells. Importantly, this dual-function discrimination strategy could obtain the precision detection of cancer cells, thereby offering assistance for improving the accuracy of early cancer diagnosis.

摘要

2019 年冠状病毒病(COVID-19)的爆发和传播导致次氯酸钠(NaOCl)消毒剂的消耗量显著增加。NaOCl 水解产生次氯酸(HOCl)以杀死病毒,这是一种在公共消毒中常用的相对高效的含氯消毒剂。虽然人们享受着 NaOCl 消毒的便利,但过度和滥用会影响水环境并威胁人类健康。重要的是,HOCl 是人体中不可或缺的活性氧(ROS)。其浓度是否正常与人体健康密切相关。体内 HOCl 过量产生会导致一些炎症性疾病甚至癌症。此外,我们注意到癌细胞中的 ROS 浓度比正常细胞高约 10 倍。在此,我们开发了一种可激活 HOCl 的生物素化双功能荧光探针 BTH。对于该探针,我们在萘酰亚胺荧光团上引入了生物素,这增加了水溶性,并通过靶向癌细胞表面过度表达的特定受体使探针在癌细胞中聚集。与 HOCl 反应后,探针的对氨基酚醚部分被氧化去除,探针的荧光得到恢复。正如预期的那样,在 pH 值为 7.4 的 PBS 溶液中,BTH 可以充分发挥检测 HOCl 的性能,并且在实际水样中检测 HOCl 浓度方面取得了成果。除此之外,BTH 通过双功能识别策略有效地区分了癌细胞和正常细胞,该策略利用生物素来使探针在癌细胞中富集,并与癌细胞中过表达的 HOCl 反应。重要的是,这种双功能识别策略可以实现对癌细胞的精确定量检测,从而有助于提高早期癌症诊断的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f30/9124045/66fe9206d512/ga1_lrg.jpg

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