Biological evaluation of a new highly sensitive and selective fluorescent probe for hypochlorous acid and its imaging application in cell and zebrafish

IF 4.7 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2025-05-01 Epub Date: 2025-03-08 DOI:10.1016/j.bioorg.2025.108358
Min Zheng , Huayan Wen , Zhengxiang Meng , Wenli Guo , Kun Wang , Miaohui Yu , Ke Li , Yun Zhang , Kechun Liu , Lei Cai , Baocun Zhu , Wenlong Sheng
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Abstract

Hypochlorous acid is one of the most widely distributed reactive oxygen species in vivo. It is usually used as a signal molecule to participate in various life activities such as immunity and metabolism, and plays a notable role in maintaining homeostasis. When hypochlorous acid level is abnormal in the body, it will lead to a variety of diseases, such as Parkinson's disease, Alzheimer's disease, atherosclerosis and cancer. Therefore, it is necessary to develop a bio-friendly fluorescent probe with fast sensitivity and specific accuracy. In this study, the innovative probe PRS owns good optical properties, sensitivity and selectivity, and the response mechanism that the generation of new bond enhanced the fluorescence intensity is studied. Biocompatibility of probe is systematically and innovatively evaluated by using cells and zebrafish models. Note that the biocompatibility valuation of probe results from cytotoxicity test, zebrafish behavioral test, hepatotoxicity test, cardiotoxicity test, nephrotoxicity test, blood vessel toxicity test, immunotoxicity test and neurotoxicity test, and experimental indicators like swimming duration, swimming distance, swimming speed, pericardial rub, fractional shortening, stroke volume, heart rate, SV-BA, shortening rate of the ventricular short axis, liver area, liver fluorescence intensity, total length of intersegmental vessels, number of vessels, and average vessel length show that the probe has good biocompatibility. Moreover, the detection performance of the probe shows that the probe can target hypochlorous acid in cell and zebrafish models. The probe is proved to be much essential for the monitoring of hypochlorous acid in vivo. Therefore, it has been proven that the meaningful detection of probe PRS for HOCl is promising in the living organism. Moreover, our innovative biocompatibility testing can be used to evaluate the biosafety of fluorescent probe as well.

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一种新型高灵敏度和选择性次氯酸荧光探针的生物学评价及其在细胞和斑马鱼中的成像应用
次氯酸是体内分布最广泛的活性氧之一。它通常作为信号分子参与免疫、代谢等各种生命活动,在维持体内平衡中起着显著作用。当体内次氯酸水平异常时,会导致多种疾病,如帕金森病、阿尔茨海默病、动脉粥样硬化和癌症。因此,有必要开发一种具有快速灵敏度和特异精度的生物友好型荧光探针。在本研究中,创新探针PRS具有良好的光学性能、灵敏度和选择性,并研究了新键生成增强荧光强度的响应机制。利用细胞和斑马鱼模型系统、创新地评价了探针的生物相容性。注意,探针的生物相容性评价来自细胞毒性试验、斑马鱼行为试验、肝毒性试验、心脏毒性试验、肾毒性试验、血管毒性试验、免疫毒性试验和神经毒性试验,以及游泳时间、游泳距离、游泳速度、心包摩擦、缩短分度、卒中量、心率、SV-BA、心室短轴缩短率、肝脏面积、肝脏荧光强度、血管总长度、血管数量和平均血管长度表明探针具有良好的生物相容性。此外,探针的检测性能表明,探针可以靶向次氯酸在细胞和斑马鱼模型。该探针被证明是监测次氯酸在体内非常必要的。因此,已经证明探针PRS对HOCl的有意义检测在生物体中是有前景的。此外,我们创新的生物相容性测试也可用于评价荧光探针的生物安全性。
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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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