Wei Yuxin, Bai Qingqing, Ning Xinlu, Bai Xiaofan, Lv Jie, Li Meng
College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China.
Postdoctoral Mobile Station of Basic Medicine, Hebei Medical University, Shijiazhuang, 050017, China.
Anal Bioanal Chem. 2025 Mar;417(6):1081-1092. doi: 10.1007/s00216-024-05683-1. Epub 2024 Dec 17.
Sensitive and accurate detection of the amyloid-β (Aβ) monomer is of fundamental significance for early diagnosis of Alzheimer's disease (AD). Herein, inspired by the specific Cu-Aβ monomer coordination, a cutting-edge colorimetric assay based on single-atom Cu anchored N-doped carbon nanospheres (Cu-NCNSs) was developed for Aβ monomer detection and an amyloidogenesis study. By directly pyrolyzing Cu-incorporated covalent organic frameworks (COFs), the resulting Cu-NCNSs with a high loading of Cu (8.04 wt %) exhibited outstanding peroxidase-like activity. The strong binding affinity of Aβ monomer to Cu-NCNSs effectively inhibited their catalytic activity, providing the basis for the colorimetric assay. The Cu-NCNSs-based sensor showed a detection limit of 1.182 nM for Aβ monomer, surpassing traditional techniques in terms of efficiency, accuracy and simplicity. Moreover, the system was successfully utilized for Aβ monomer detection in rat cerebrospinal fluid (CSF). Notably, the distinct inhibitory effects of monomeric and aggregated Aβ species on the catalytic activity of Cu-NCNSs were allowed for monitoring of the dynamic aggregation process of Aβ. Compared to thioflavin T (ThT), the most widely used amyloid dye, the detection system exhibited greater sensitivity towards toxic Aβ oligomers, which was crucial for early AD diagnosis and treatment. Our work not only sheds light on the rational design of highly active single-atom nanozymes from COFs but also expands the potential applications of nanozymes in early disease diagnosis.
灵敏且准确地检测淀粉样β蛋白（Aβ）单体对于阿尔茨海默病（AD）的早期诊断具有重要意义。在此，受特定的铜 - Aβ单体配位作用启发，开发了一种基于单原子铜锚定的氮掺杂碳纳米球（Cu - NCNSs）的前沿比色法，用于Aβ单体检测和淀粉样蛋白生成研究。通过直接热解含铜的共价有机框架（COFs），得到的具有高铜负载量（8.04 wt%）的Cu - NCNSs表现出出色的过氧化物酶样活性。Aβ单体与Cu - NCNSs的强结合亲和力有效抑制了它们的催化活性，为比色法提供了基础。基于Cu - NCNSs的传感器对Aβ单体的检测限为1.182 nM，在效率、准确性和简便性方面超过了传统技术。此外，该系统成功用于大鼠脑脊液（CSF）中Aβ单体的检测。值得注意的是，单体和聚集态Aβ物种对Cu - NCNSs催化活性的不同抑制作用使得能够监测Aβ的动态聚集过程。与最广泛使用的淀粉样蛋白染料硫黄素T（ThT）相比，该检测系统对有毒的Aβ寡聚体表现出更高的灵敏度，这对于AD的早期诊断和治疗至关重要。我们的工作不仅为从COFs合理设计高活性单原子纳米酶提供了思路，还扩展了纳米酶在疾病早期诊断中的潜在应用。
