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用于活细胞和炎症小鼠模型中一氧化氮检测与成像的合理构建的荧光纳米传感器

Rationally Constructed Fluorescent Nanosensor for Nitric Oxide Detection and Imaging in Living Cells and Inflammatory Mice Models.

作者信息

Yang Qiaomei, Zhou Yizhuang, Tan Libin, Xie Can, Luo Kun, Li Xiaowen, Zeng Miao, Zhou Liyi

机构信息

College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.

The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health, Guilin Medical University, Guilin, Guangxi 541001, China.

出版信息

Anal Chem. 2023 Jan 31;95(4):2452-2459. doi: 10.1021/acs.analchem.2c04640. Epub 2023 Jan 19.

DOI:10.1021/acs.analchem.2c04640
PMID:36657472
Abstract

For the early diagnosis and effective evaluation of treatment effects of inflammation, a bioanalytical method is urgently needed to monitor the metabolite nitric oxide (NO) associated with inflammatory diseases. However, developing a reliable detection method with excellent water solubility, biocompatibility, long retention time, and blood circulation is still challenging. In this work, we reported for the first time a host-guest self-assembled nanosensor CTA for the quantitative detection and visualization of NO levels in inflammatory models. CTA mainly consists of two parts: (i) an adamantyl-labeled guest small-molecule RN-adH containing a classical response moiety phenylenediamine for a chemical-specific response toward NO and fluorophore rhodamine B with excellent optical properties as an internal reference for self-calibration and (ii) a remarkable water-soluble and biocompatible supramolecular β-cyclodextrin polymer (Poly-β-CD) host. In the presence of NO, the phenylenediamine unit was reacted with NO at a low pH value of ∼7.0, accompanied by changes in the intensity of the two emission peaks corrected for each other and the change in fluorescence color of the CTA solution from fuchsia to pink. Furthermore, CTA was an effective tool for NO detection with a fast response time (∼60 s), high selectivity, and sensitivity (LOD: 22.3 nM). Impressively, the CTA nanosensor has successfully achieved the targeted imaging of NO in living inflammatory RAW 264.7 cells and mice models with satisfactory results, which can provide a powerful molecular tool for the visualization and assessment of the occurrence and development of NO-related inflammatory diseases in complex biosystems.

摘要

为了实现炎症的早期诊断和治疗效果的有效评估,迫切需要一种生物分析方法来监测与炎症性疾病相关的代谢产物一氧化氮(NO)。然而,开发一种具有优异水溶性、生物相容性、长保留时间和血液循环能力的可靠检测方法仍然具有挑战性。在这项工作中,我们首次报道了一种主客体自组装纳米传感器CTA,用于定量检测和可视化炎症模型中的NO水平。CTA主要由两部分组成:(i)一个金刚烷基标记的客体小分子RN-adH,它含有一个用于对NO进行化学特异性响应的经典反应基团苯二胺,以及具有优异光学性质的荧光团罗丹明B作为自校准的内部参考;(ii)一种卓越的水溶性和生物相容性超分子β-环糊精聚合物(聚-β-CD)主体。在NO存在的情况下,苯二胺单元在pH值约为7.0的低pH条件下与NO发生反应,同时两个相互校正的发射峰强度发生变化,CTA溶液的荧光颜色从紫红色变为粉红色。此外,CTA是一种用于NO检测的有效工具,具有快速响应时间(约60秒)、高选择性和灵敏度(检测限:22.3 nM)。令人印象深刻的是,CTA纳米传感器已成功实现了在活的炎症RAW 264.7细胞和小鼠模型中对NO的靶向成像,结果令人满意,这可为可视化和评估复杂生物系统中与NO相关的炎症性疾病的发生和发展提供强大的分子工具。

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