A dual-functional fluorescence probe for detection of Aβ aggregates and hydroxyl radicals
A dual-functional fluorescence probe for detection of Aβ aggregates and hydroxyl radicals
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DOI：
10.1016/j.snb.2023.134653
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发表时间：
2023-12
期刊：
影响因子：
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通讯作者：
Yan An;Xue Luo;Shuangshuang Wei;Jia-jia Lv;Jie Gao;Xinmin Li;Min Yang;Junjun Luo;
中科院分区：
文献类型：
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作者：
Yan An;Xue Luo;Shuangshuang Wei;Jia-jia Lv;Jie Gao;Xinmin Li;Min Yang;Junjun Luo;
同步检测Aβ聚集体和活性氧（ROS）将为揭示两种关键阿尔茨海默病（AD）标志之间的复杂关系提供直接的见解。本文开发了首个用于双功能检测Aβ聚集体和高破坏性ROS羟基自由基（•OH）的荧光探针（Quin-HCy）。Quin-HCy设计具有血脑屏障（BBB）渗透性喹啉荧光团和•oh响应氢菁部分。Quin-HCy分别在450 nm和770 nm处对Aβ聚集体和•OH有明显的荧光响应。大光谱位移（~ 320 nm）有利于在两个遥远的通道中独立检测这两种分析物。Quin-HCy通过添加Fenton试剂、PMA刺激和诱导铁下垂来成像细胞中的•OH。最重要的是，Quin-HCy荧光成像显示，在Aβ聚集物处理的神经元细胞中产生了显著的•OH，这为Aβ聚集物与•OH在AD病因学中的高度依赖性提供了直接证据。此外，quinn - hcy具有良好的血脑屏障通透性，能够在AD小鼠脑切片中成像Aβ斑块和•OH。
Synchronous detection of Aβ aggregates and reactive oxygen species (ROS) would provide direct insight to reveal the complicated correlations between the two crucial Alzheimer’s disease (AD) hallmarks. Herein, the first fluorescence probe (Quin-HCy) for dual-functional detection of Aβ aggregates and the highly destructive ROS hydroxyl radicals (•OH) is developed. Quin-HCy is designed with a blood-brain barrier (BBB) permeable quinoline fluorophore and a •OH-responsive hydrocyanine moiety. Quin-HCy shows obvious fluorescence increases in response to Aβ aggregates and •OH at 450 nm and 770 nm, respectively. The large spectral shift (∼ 320 nm) is advantageous for the independent detection of these two analytes in two distant channels. Quin-HCy has been used to image •OH in cells through the addition of Fenton reagents, stimulation with PMA and induction of ferroptosis. Most importantly, fluorescence imaging with Quin-HCy shows that significant •OH is generated in Aβ aggregate-treated neuron cells, which provides direct evidence for the high dependence between Aβ aggregates and •OH in the etiology of AD. Besides, Quin-HCy has favorable BBB permeability, and is able to image Aβ plaques and •OH in AD mice brain slices.