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用于靶向监测和抑制β-淀粉样蛋白寡聚体的基于二硫化钼纳米片的荧光“关-开”探针。

Molybdenum disulfide nanosheets-based fluorescent "off-to-on" probe for targeted monitoring and inhibition of β-amyloid oligomers.

作者信息

Kong Lingna, Zhou Xinguang, Shi Guoyue, Yu Yanyan

机构信息

School of Chemistry and Molecular Engineering, Shanghai Key Laboratory for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China.

出版信息

Analyst. 2020 Sep 28;145(19):6369-6377. doi: 10.1039/d0an00019a.

DOI:10.1039/d0an00019a
PMID:32729592
Abstract

A novel and simple "off-to-on" fluorescent sensing platform for β-amyloid oligomers (Aβo) was developed based on dye (FAM)-labeled single-strand DNA (FAM-ssDNA)-conjugated molybdenum disulfide nanosheets (MoS2 NSs). Due to strong adsorption of ss-DNA to the surface of MoS2 NSs, the fluorescence of FAM was quenched remarkably, leading to a fluorescent "off" state. However, in the presence of Aβo, a hybrid structure between Aβo and FAM-ssDNA resulted in the dissociation of FAM-ssDNA from MoS2 NSs and an obvious fluorescence recovery transformed the fluorescence to an "on" state. The developed fluorescence sensing assay showed a good linear relationship toward Aβo ranging from 0.01 to 20 μM (R2 = 0.994) with a satisfactory detection limit of 3.1 nM. Practical samples of hippocampus and cortex tissues from APP/PS1 double transgenic AD mice were applied to demonstrate feasibility of the assay. Moreover, we found that similar to MoS2 nanoparticles, MoS2 NSs possessed therapeutic effects on Alzheimer's disease (AD) by inhibiting Aβ aggregations and degrading the previously formed Aβ fibrils. Collectively, the high sensitivity, specificity, and good biocompatibility along with an efficient anti-aggregation ability, the presented fluorescent strategy with MoS2 NSs demonstrated their promising potential for future AD-related research.

摘要

基于染料(FAM)标记的单链DNA(FAM-ssDNA)共轭二硫化钼纳米片(MoS2 NSs),开发了一种新颖且简单的用于β-淀粉样蛋白寡聚体(Aβo)的“关-开”荧光传感平台。由于单链DNA对MoS2 NSs表面的强烈吸附,FAM的荧光被显著淬灭,导致荧光“关”状态。然而,在Aβo存在的情况下,Aβo与FAM-ssDNA之间形成的杂化结构导致FAM-ssDNA从MoS2 NSs上解离,荧光明显恢复,使荧光转变为“开”状态。所开发的荧光传感测定法对Aβo在0.01至20 μM范围内呈现良好的线性关系(R2 = 0.994),检测限低至3.1 nM,令人满意。应用APP/PS1双转基因AD小鼠的海马和皮质组织实际样本证明了该测定法的可行性。此外,我们发现与二硫化钼纳米颗粒类似,MoS2 NSs通过抑制Aβ聚集和降解先前形成的Aβ纤维对阿尔茨海默病(AD)具有治疗作用。总体而言,具有高灵敏度、特异性和良好生物相容性以及高效抗聚集能力,所提出的基于MoS2 NSs的荧光策略在未来AD相关研究中显示出有前景的潜力。

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