Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques
Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques
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DOI：
10.1021/acschemneuro.2c00468
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发表时间：
2023-02-07
影响因子：
5
通讯作者：
Xu, Ming-Hua
中科院分区：
文献类型：
--
作者：
Cao, Yangyang;Liu, Xiaohui;Xu, Ming-Hua
淀粉样蛋白- β (A β)是老年斑的核心组成蛋白，是阿尔茨海默病（AD）的关键病理标志之一。在这里，我们描述了香豆素衍生的小分子荧光团用于A β成像的设计、合成和评价。通过将芳香香豆素框架嵌入推拉发色团的π桥中，发现了一种适用于a β高效识别的新型荧光探针XCYC-3。XCYC-3对聚集的A β比单体A β表现出更高的荧光增强，具有良好的血脑屏障通透性。体外染色和体内成像研究表明，XCYC-3能有效识别AD转基因小鼠脑内的A β斑块。这些结果表明，XCYC-3是一种很有前景的a β荧光显像剂，可能为未来开发有效的a β近红外荧光探针提供重要线索。
Amyloid-beta (A beta) is the core constituent protein of senile plaques, which is one of the key pathological hallmarks of Alzheimer's disease (AD). Here we describe the design, synthesis, and evaluation of coumarin-derived small molecule fluorophores for A beta imaging. By embedding the aromatic coumarin framework into pi bridge of a push-pull chromophore, a novel fluorescence probe XCYC-3 applicable to efficient A beta recognition was discovered. XCYC-3 displays higher fluorescent enhancement for aggregated A beta than monomeric A beta, and possesses good blood-brain barrier permeability. In vitro staining and in vivo imaging studies demonstrated that XCYC-3 could efficiently recognize A beta plaques in the brain of AD transgenic mice. These results suggest that XCYC-3 is a promising fluorescence imaging agent for A beta, which might provide important clues for the future development of potent NIR fluorescent probes for A beta diagnosis.