Aβ蛋白近红外快速荧光探针的设计与合成

IF 4.1 3区工程技术 Q2 CHEMISTRY, APPLIED

Dyes and Pigments Pub Date : 2025-04-18 DOI:10.1016/j.dyepig.2025.112844

Pengbo She , Lei Xing , Mingyang Zhou , Shu Xing , Yaozheng Yang , Xiuxiu Li , Xuanxuan Ma , Tao Cheng , Jinjian Wei , John K. Bielicki , Jing Xu

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引用次数: 0

摘要

利用近红外荧光探针检测阿尔茨海默病（AD）中的淀粉样蛋白-β (Aβ)已经得到了广泛的研究。然而，开发能够同时满足快速、准确和视觉检测要求的探针仍然具有挑战性。本研究设计了一种基于D-π-A结构框架的新型a β靶向荧光探针NQM-FN。NQM-FN以喹啉-丙二腈（QM）为荧光组分，N，N-二甲基胺为识别单元。采用推挽式电子偶联体系（以N，N-二甲基为电子供体）；作为电子受体的磺酸和氰化物基团)，NQM-FN诱导近红外发射并增强血脑屏障（BBB）的渗透率。荧光分析表明，由于聚集引起的猝灭（ACQ）， NQM-FN在水环境中不发光，但在有机溶剂（如乙醇）中表现出强大的荧光。当结合到Aβ聚集体时，构象刚性抑制扭曲的分子内电荷转移（TICT），促进快速的“开关”检测，增加发射强度。NQM-FN与PBS溶液中的a - β42聚集体相互作用，显示出快速的“开关”（大约10秒）。MTT实验显示，NQM-FN探针具有良好的细胞相容性，维持超过80%的细胞存活率。共聚焦激光扫描显微镜（CLSM）成像证实，使用NQM-FN探针可以成功地实时、灵敏、视觉地检测活细胞内的Aβ42聚集体。本研究介绍了一种用于检测a β42聚集体的荧光探针的合成方法，所开发的NQM-FN探针作为荧光检测工具具有很大的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Design and synthesis of “off-on” fluorescent probes with rapid near-infrared time responsivity for Aβ protein

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Design and synthesis of “off-on” fluorescent probes with rapid near-infrared time responsivity for Aβ protein

The utilization of near-infrared fluorescent probes for the detection of amyloid-β (Aβ) in Alzheimer's disease (AD) has been extensively investigated. Nevertheless, the development of probes that can simultaneously meet the requirements for rapid, accurate, and visual detection remains challenging. In this study, a novel Aβ-targeted fluorescent probe, designated NQM-FN, has been designed based on a D-π-A structural framework. NQM-FN incorporates quinoline-malononitrile (QM) as the fluorescent component and N,N-dimethylmino as the recognition unit. By utilizing a push-pull electronic conjugation system (with N,N-dimethylmino as electron donor; sulfonic acid and cyanide groups as electron acceptors), NQM-FN induces near-infrared emission and enhances blood-brain barrier (BBB) permeability. Fluorescence analysis indicated that NQM-FN is non-emissive in aqueous environments due to aggregation-caused quenching (ACQ), yet it demonstrates robust fluorescence in organic solvents, such as ethanol. When bound to Aβ aggregates, conformational rigidification suppresses twisted intramolecular charge transfer (TICT), facilitating rapid ‘off-on’ detection with increased emission intensity. NQM-FN interacts with Aβ42 aggregates in PBS solution, showing a rapid “off-on” switch (approximately 10 s). MTT assays revealed that the NQM-FN probe has good cellular compatibility, sustaining over 80 % cell viability. Confocal laser scanning microscopy (CLSM) imaging confirmed the successful real-time, sensitive, and visual detection of Aβ42 aggregates within live cells using the NQM-FN probe. This research introduces an innovative method for synthesizing fluorescent probes for the detection of Aβ42 aggregates, and the developed NQM-FN probe shows great promise as a tool for fluorescent detection.

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来源期刊

Dyes and Pigments 工程技术-材料科学：纺织

CiteScore

8.20

自引率

13.30%

发文量

933

审稿时长

33 days

期刊介绍： Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied. Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media. The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.