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一种基于脂质体的适体传感器,集成了竞争反应,可实现 Aβ 寡聚物的便携式电化学检测。

A liposome-based aptasensor integrated with competitive reaction enabling portable and electrochemical detection of Aβ oligomer.

机构信息

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, PR China.

Shenzhen NTEK Testing Technology Co., Ltd., Shenzhen, 518000, Guangdong, PR China.

出版信息

Biosens Bioelectron. 2023 Apr 1;225:115108. doi: 10.1016/j.bios.2023.115108. Epub 2023 Jan 26.

Abstract

Aggregation of β-amyloid (Aβ) were considered as a typical pathological feature of Alzheimer's disease (AD). Extensive studies have verified that soluble Aβ oligomers (AβO) were more toxic to neurons than plaques. Herein, in this work, a glucose entrapped liposome-based portable aptasensor was fabricated for recognizing and interacting with AβO by specific aptamer on liposome (G-Lip-Apt). Then, a single strand DNA, designed to be partially complementary to AβO aptamer, was modified on amino-functionalized FeO@SiO to obtain a magnetic nanocomposite (FeO@SiO/NH-DNA). In the presence of AβO, the specific recognition between AβO and its aptamer on G-Lip-Apt made AβO bounded with G-Lip-Apt. With subsequent introduction of FeO@SiO/NH-DNA, the unreacted G-Lip-Apt was further linked with FeO@SiO/NH-DNA by double stranded complementary pairing interaction. Along with the addition of TritonX-100 into the formed G-Lip-Apt/FeO@SiO/NH-DNA complex, the encapsulated glucose was released from liposome and then measured by a personal glucose meter (PGM). Good linear correlation was acquired over concentration of 5.0-1000 nM and the limit of detection (LOD) was calculated to be 2.27 nM for AβO. The developed portable electrochemical strategy integrated magnetic separation, competitive reaction and point of care test (POCT) to achieve high sensitivity, selectivity and accuracy, therefore enabled it successfully applied to the analysis of AβO in the hippocampus and cortex of APP/PS1 transgenic AD mice.

摘要

β-淀粉样蛋白 (Aβ) 的聚集被认为是阿尔茨海默病 (AD) 的典型病理特征。大量研究已经证实,可溶性 Aβ 寡聚体 (AβO) 比斑块对神经元的毒性更大。在这项工作中,本文制备了一种基于葡萄糖包封脂质体的便携式适体传感器,通过脂质体上的特异性适体 (G-Lip-Apt) 识别和与 AβO 相互作用。然后,设计了一条与 AβO 适体部分互补的单链 DNA,并修饰在氨基功能化的 FeO@SiO 上,得到磁性纳米复合材料 (FeO@SiO/NH-DNA)。在 AβO 的存在下,AβO 与其在 G-Lip-Apt 上的适体之间的特异性识别使得 AβO 与 G-Lip-Apt 结合。随后引入 FeO@SiO/NH-DNA,未反应的 G-Lip-Apt 通过双链互补配对相互作用进一步与 FeO@SiO/NH-DNA 连接。随着 TritonX-100 加入到形成的 G-Lip-Apt/FeO@SiO/NH-DNA 复合物中,包封的葡萄糖从脂质体中释放出来,然后用个人血糖仪 (PGM) 进行测量。在 5.0-1000 nM 的浓度范围内获得了良好的线性相关性,AβO 的检测限 (LOD) 计算为 2.27 nM。所开发的便携式电化学策略集成了磁性分离、竞争反应和即时检测 (POCT),以实现高灵敏度、选择性和准确性,因此成功应用于 APP/PS1 转基因 AD 小鼠海马和皮质中 AβO 的分析。

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