School of Physical Sciences, Jawaharlal Nehru University, New Delhi, India.
Cognitive Neuroimaging Centre, Nanyang Technological University (NTU), Singapore, Singapore.
Int J Nanomedicine. 2024 Aug 14;19:8271-8284. doi: 10.2147/IJN.S446212. eCollection 2024.
Development of SERS-based Raman nanoprobes can detect the misfolding of Amyloid beta (Aβ) 42 peptides, making them a viable diagnostic technique for Alzheimer's disease (AD). The detection and imaging of amyloid peptides and fibrils are expected to help in the early identification of AD.
Here, we propose a fast, easy-to-use, and simple scheme based on the selective adsorption of Aβ42 molecules on SERS active gold nanoprobe (RB-AuNPs) of diameter 29 ± 3 nm for Detection of Alzheimer's Disease Biomarkers. Binding with the peptides results in a spectrum shift, which correlates with the target peptide. We also demonstrated the possibility of using silver nanoparticles (AgNPs) as precursors for the preparation of a SERS active nanoprobe with carbocyanine (CC) dye and AgNPs known as silver nanoprobe (CC-AgNPs) of diameter 25 ± 4 nm.
RB-AuNPs probe binding with the peptides results in a spectrum shift, which correlates with the target peptide. Arginine peak appears after the conjugation confirms the binding of Aβ 42 with the nanoprobe. Tyrosine peaks appear after conjugated Aβ42 with CC-AgNPs providing binding of the peptide with the probe. The nanoprobe produced a strong, stable SERS signal. Further molecular docking was utilized to analyse the interaction and propose a structural hypothesis for the process of binding the nanoprobe to Aβ42 and Tau protein.
This peptide-probe interaction provides a general enhancement factor and the molecular structure of the misfolded peptides. Secondary structural information may be obtained at the molecular level for specific residues owing to isotope shifts in the Raman spectra. Conjugation of the nanoprobe with Aβ42 selectively detected AD in bodily fluids. The proposed nanoprobes can be easily applied to the detection of Aβ plaques in blood, saliva, and sweat samples.
基于 SERS 的拉曼纳米探针的开发可以检测淀粉样β（Aβ）42 肽的错误折叠，使其成为阿尔茨海默病（AD）的可行诊断技术。预计对淀粉样肽和原纤维的检测和成像将有助于早期识别 AD。
在这里，我们提出了一种快速、易用且简单的方案，该方案基于 Aβ42 分子在直径为 29±3nm 的 SERS 活性金纳米探针（RB-AuNPs）上的选择性吸附，用于检测阿尔茨海默病生物标志物。与肽结合会导致与靶肽相关的光谱位移。我们还证明了使用银纳米粒子（AgNPs）作为前体制备具有碳菁（CC）染料和 AgNPs 的 SERS 活性纳米探针的可能性，AgNPs 被称为直径为 25±4nm 的银纳米探针（CC-AgNPs）。
RB-AuNPs 探针与肽结合会导致与靶肽相关的光谱位移。与纳米探针结合后精氨酸峰的出现证实了 Aβ42 与纳米探针的结合。与 CC-AgNPs 共轭的 Aβ42 出现酪氨酸峰，提供了肽与探针的结合。该纳米探针产生了强而稳定的 SERS 信号。进一步利用分子对接分析了相互作用，并提出了一个结构假设，用于纳米探针与 Aβ42 和 Tau 蛋白结合的过程。
这种肽-探针相互作用提供了一般的增强因子和错误折叠肽的分子结构。由于拉曼光谱中的同位素位移，可以在分子水平上获得特定残基的二级结构信息。纳米探针与 Aβ42 的共轭选择性地检测体液中的 AD。所提出的纳米探针可以很容易地应用于血液、唾液和汗液样本中 Aβ 斑块的检测。
