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碳点敏化镧系无限配位聚合物纳米粒子:用于阿尔茨海默病生物标志物脑脊髓液 Aβ单体的比率荧光传感

Carbon dots sensitized lanthanide infinite coordination polymer nanoparticles: Towards ratiometric fluorescent sensing of cerebrospinal Aβ monomer as a biomarker for Alzheimer's disease.

机构信息

School of Ecological and Environmental Sciences, Shanghai Key Lab for Urban Ecological Process and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China; Institute of Eco-Chongming, 3663 Zhongshan Road, Shanghai, 200062, China.

School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

出版信息

Anal Chim Acta. 2020 Apr 8;1105:147-154. doi: 10.1016/j.aca.2020.01.021. Epub 2020 Jan 11.

DOI:10.1016/j.aca.2020.01.021
PMID:32138913
Abstract

Herein, a novel ratiometric fluorescent probe based on CDs@Eu/GMP ICP nanoparticles was developed for the detection of Aβ monomer in rat as a biomarker for Alzheimer's disease (AD) by fully exploring the competitive coordination interaction and by taking advantage of excellent optical property of carbon dots sensitized lanthanide infinite coordination polymer (ICP) nanoparticles. The carbon dots (CDs) with abundant functional groups were encapsulated into Eu/GMP ICPs through self-adaptive chemistry, which could not only sensitize the red fluorescence of Eu/GMP ICPs effectively, but also act as an internal reference for self-correction. In the absence of Cu, the as-formed CDs@Eu/GMP ICPs exhibited the characteristic emission of CDs at 400 nm and strong emission of Eu at 592 nm, 615 nm, 650 nm and 694 nm. With the addition of Cu, the red fluorescence of Eu decreased due to the coordination interaction between CDs and Cu, thus destroyed the antenna effect. After the subsequent addition of Aβ monomer, the specific binding occurred between Cu and Aβ monomer, and then the red fluorescence of Eu restored again. During this process, the fluorescence of CDs remained unchanged, thus could be used as an internal reference to cancel out the environmental fluctuation and was more adaptive for the detection of Aβ monomer in biological fluids. The method demonstrated here was highly sensitive, free from the interference of other species in rat brain, the in vivo analysis of Aβ monomer in CSF and different brain regions from normal rats and Alzheimer's rats could be realized, which was of great significance for better understanding the mechanism of AD and paving the way to understand the chemical essence involved in AD.

摘要

本文开发了一种基于 CDs@Eu/GMP ICP 纳米粒子的新型比率荧光探针,通过充分利用碳点敏化镧系无限配位聚合物(ICP)纳米粒子的优异光学性质和竞争配位相互作用,用于检测大鼠中的 Aβ单体作为阿尔茨海默病(AD)的生物标志物。具有丰富官能团的碳点(CDs)通过自适应化学被包裹到 Eu/GMP ICP 中,这不仅可以有效地敏化 Eu/GMP ICP 的红色荧光,还可以作为自校正的内参。在不存在 Cu 的情况下,形成的 CDs@Eu/GMP ICP 表现出 400nm 处的 CDs 特征发射和 592nm、615nm、650nm 和 694nm 处的 Eu 强发射。随着 Cu 的加入,由于 CDs 和 Cu 之间的配位相互作用,Eu 的红色荧光降低,从而破坏了天线效应。随后加入 Aβ单体后,Cu 与 Aβ单体发生特异性结合,Eu 的红色荧光恢复。在此过程中,CDs 的荧光保持不变,因此可以用作内参来消除环境波动,更适合检测生物流体中的 Aβ单体。该方法具有很高的灵敏度,不受大鼠脑内其他物质的干扰,能够实现正常大鼠和阿尔茨海默病大鼠脑脊液和不同脑区中 Aβ单体的体内分析,这对于更好地理解 AD 的机制和为理解 AD 涉及的化学本质铺平道路具有重要意义。

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