On-exosome-membrane DNA polymerization-powered magneto-electrochemical aptasensing for osteosarcoma

IF 6.1 2区化学 Q1 CHEMISTRY, ANALYTICAL

Analytica Chimica Acta Pub Date : 2026-03-08 Epub Date: 2026-01-16 DOI:10.1016/j.aca.2026.345093

Guang-Xian Zhong , Huang-Feng Lin , Fei-Huan Fu , Jing-Wei Zhou , Chong-Yu Chen , Chao-Yang Wu , Jian-Ping Lin , Xiong-Wei Xu , Jian-Hua Lin , Jin-Yuan Chen

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引用次数: 0

Abstract

Background

The development of exosomes-based non-invasive liquid biopsy method is essential for an early diagnosis of cancers such as osteosarcoma (OS). The emerging isothermal nucleic acid amplification (NAA)-integrated electrochemical aptasensor (E-aptasensor) holds a great promise due to its affordability, rapid response, high sensitivity, and multiplexing capability. However, these aptasensors often require a challenging and complicated integration of signal trigger sequences into the parent aptamers that regulates the NAA. Thus, it is highly desirable to develop a template-free and universal isothermal NAA-intergrated E-aptasensor for OS-derived exosome detection.

Results

Herein, via terminal deoxynucleotidyl transferase (TdTase)-mediated DNA polymerization on exosome membrane, we firstly proposed a membrane-initiated enzymatic polymerization (MIEP)-based magneto-driven E-aptasensor for an ultrasensitive detection of OS cell-derived exosomes. Specifically, the LC09 aptamers-modified magnetic microbeads (MMBs) efficiently captured the specific exosomes. Afterwards, the direct on-exosome membrane DNA polymerization was performed by TdTase and then large amounts of horseradish peroxidases were bound via immunoreaction, leading to a strong catalytic current in the substrate of 3,3′,5,5′-tetramethylbenzidine/hydrogen peroxide on the surface of a magnetic glassy carbon electrode. This MIEP-based E-aptasensor reported a satisfactory detection result, displaying a broad linear range (6 × 10⁷∼6 × 10¹⁰ particles/mL), a low detection limit (60 particles/μL), a good specificity toward other tumor cell-derived exosomes, and a good recovery (87.9 %–98.3 % in human plasma). Finally, this method was applied to different clinical samples of micro-volume plasma and distinguished them successfully.

Significance

The proposed aptasensor can serve as a powerful and potential tool for liquid biopsy of OS, owing to its high generality, low sample demand, and high practicability. Furthermore, the innovative design strategy established in this work provides a new and versatile avenue for the construction of advanced exosome biosensors, thereby broadening their application in clinical research and precision medicine.

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外泌体膜DNA聚合驱动的磁电化学适体感应治疗骨肉瘤

基于外泌体的非侵入性液体活检方法的发展对于骨肉瘤（OS）等癌症的早期诊断至关重要。新兴的等温核酸扩增（NAA）集成电化学aptassensor （e - aptassensor）因其价格合理、反应速度快、灵敏度高、多路复用等优点，具有广阔的应用前景。然而，这些适体传感器通常需要将信号触发序列整合到调节NAA的亲本适体中，这具有挑战性和复杂性。因此，开发一种无模板的通用等温naa集成e- aptassensor用于os衍生的外泌体检测是非常必要的。结果在本文中，通过末端脱氧核苷酸转移酶（TdTase）介导的外泌体膜DNA聚合，我们首次提出了一种基于膜启动酶促聚合（MIEP）的磁驱动e-适体传感器，用于超灵敏检测OS细胞来源的外泌体。具体来说，LC09适配体修饰的磁微珠（MMBs）有效地捕获了特定的外泌体。然后，通过TdTase直接在外泌体膜上进行DNA聚合，然后通过免疫反应结合大量的辣根过氧化物酶，在磁性玻璃碳电极表面的3,3 ',5,5 ' -四甲基联苯胺/过氧化氢底物中产生强催化电流。该基于miep的e - aptas传感器报告了令人满意的检测结果，显示出宽的线性范围（6×107 ~ 6×1010颗粒/mL），低检测限（60颗粒/μL），对其他肿瘤细胞来源的外泌体具有良好的特异性，并且回收率良好（人血浆中87.9% ~ 98.3%）。最后，将该方法应用于临床不同的微体积血浆样品，并成功地进行了区分。本文提出的适体传感器具有通用性强、样本量少、实用性强等优点，可作为OS液体活检的有力工具。此外，本研究建立的创新设计策略为构建先进的外泌体生物传感器提供了一条新的、通用的途径，从而扩大了其在临床研究和精准医学中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Analytica Chimica Acta 化学-分析化学

CiteScore

10.40

自引率

6.50%

发文量

1081

审稿时长

38 days

期刊介绍： Analytica Chimica Acta has an open access mirror journal Analytica Chimica Acta: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Analytica Chimica Acta provides a forum for the rapid publication of original research, and critical, comprehensive reviews dealing with all aspects of fundamental and applied modern analytical chemistry. The journal welcomes the submission of research papers which report studies concerning the development of new and significant analytical methodologies. In determining the suitability of submitted articles for publication, particular scrutiny will be placed on the degree of novelty and impact of the research and the extent to which it adds to the existing body of knowledge in analytical chemistry.