Tao Cheng, Peifen Lu, Yixi Dong, Jiabao Yu, Gang Wang, Jianwei Jiao, Peng Miao, Jin Jiao
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引用次数: 0
摘要
本文开发了一种顺序响应肽 DNA 双语纳米生物传感器,可对淀粉样蛋白信号通路进行综合定量。在该系统中,上游的β位淀粉样前体蛋白切割酶1(BACE1)蛋白酶和下游的Aβ寡聚体(AβO)被设计为AND DNA逻辑门的两个输入端。在两个输入端同时存在的情况下,带有适配体的多肽底物可以依次被裂解,从而产生电化学和荧光双模式输出。与传统的基于多肽纳米技术的单一蛋白酶活性检测相比,该策略可准确诊断正常人与阿尔茨海默病(AD)。更重要的是,它还能实现对阿尔茨海默病和 2 型糖尿病患者的鉴别诊断。这种双语纳米生物传感器成功应用于检测 BACE1(1-100 U mL-1)和 AβO(5-1000 pg mL-1),检测限分别低至 0.10 U mL-1 和 0.76 pg mL-1。此外,这种策略还启发了针对其他信号通路激活的先进纳米生物传感器,它们是未来生物学和医学研究的潜在工具。
A Bilingual Nanobiosensor for Cross-Category Integrated Decoding of the Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1–Aβ Oligomer Signaling Pathway
Herein, a sequentially responsive peptide DNA bilingual nanobiosensor is developed, which allows integrated quantification of amyloid signaling pathway. In this system, upstream beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protease and downstream Aβ oligomer (AβO) are designed as two inputs for the AND DNA logic gate. In the existence of both inputs, peptide substrate with aptamer can be sequentially cleaved, reporting electrochemical and fluorescence dual-mode outputs. In comparison with conventional single protease activity assay based on peptide nanotechnology, this strategy permits accurate diagnosis of Alzheimer's disease (AD) from normal subjects. More importantly, it can achieve distinguished diagnosis between AD and type 2 diabetes mellitus patients. This bilingual nanobiosensor is successfully applied to detect BACE1 (1–100 U mL−1) and AβO (5–1000 pg mL−1) with limit of detections as low as 0.10 U mL−1 and 0.76 pg mL−1, respectively. Furthermore, this strategy inspires advanced nanobiosensors to target the activation of other signaling pathways, which are potential tools for future biology and medicine investigation.