Multi-protein-triggered, aptamer-tethered auto-cycling proximity recorder in formalin-fixed paraffin-embedded tissues

IF 2.6 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Analytical biochemistry Pub Date : 2025-07-08 DOI:10.1016/j.ab.2025.115940

Xiaofang Zheng , Daikun Zheng , Linfeng Zheng , Peng Wang , Yong Liu , Xixi You , Xiaoling Zheng , Xinyuan Cao , Jiao Luo , Wansong Chen , Guoli Li , Ruizi Peng

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Abstract

Unraveling tumor-associated membrane proteins' spatial proximity holds a significance for clinically relevant multiple biomarker detection. Herein, based on aptamer binding to target proteins in clinical formalin-fixed paraffin-embedded (FFPE) tissue samples, we developed aptamer-tethered auto-cycling proximity recording (APR) probes as a proof-of-concept methodology for biosensing membrane proteins' spatial proximity. This APR enables continuous and repetitive recording of spatial neighboring pairs of DNA probes in FFPE breast cancer tissue samples in situ, without altering the probes themselves. Finally, this aptamer-based auto-cycling proximity recorder is able to identify spatial proximity of three membrane proteins in FFPE breast cancer tissues. Our research establishes a foundation for proximity-driven biosensing platform and provides a perspective for exploration in aptamer-based bioimaging in clinical tissue samples.

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福尔马林固定石蜡包埋组织中多蛋白触发、适配体系住的自动循环接近记录仪

揭示肿瘤相关膜蛋白的空间接近性对临床相关的多种生物标志物检测具有重要意义。在此，基于适体与临床福尔马林固定石蜡包埋（FFPE）组织样本中靶蛋白的结合，我们开发了适体系住的自动循环接近记录（APR）探针，作为生物传感膜蛋白空间接近的概念验证方法。该APR能够在原位连续重复记录FFPE乳腺癌组织样本中的空间相邻DNA探针对，而不改变探针本身。最后，这种基于适配体的自动循环接近记录器能够识别FFPE乳腺癌组织中三种膜蛋白的空间接近性。我们的研究为接近驱动的生物传感平台奠定了基础，并为临床组织样本中基于适配体的生物成像的探索提供了前景。

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来源期刊

Analytical biochemistry 生物-分析化学

CiteScore

5.70

自引率

0.00%

发文量

283

审稿时长

44 days

期刊介绍： The journal''s title Analytical Biochemistry: Methods in the Biological Sciences declares its broad scope: methods for the basic biological sciences that include biochemistry, molecular genetics, cell biology, proteomics, immunology, bioinformatics and wherever the frontiers of research take the field. The emphasis is on methods from the strictly analytical to the more preparative that would include novel approaches to protein purification as well as improvements in cell and organ culture. The actual techniques are equally inclusive ranging from aptamers to zymology. The journal has been particularly active in: -Analytical techniques for biological molecules- Aptamer selection and utilization- Biosensors- Chromatography- Cloning, sequencing and mutagenesis- Electrochemical methods- Electrophoresis- Enzyme characterization methods- Immunological approaches- Mass spectrometry of proteins and nucleic acids- Metabolomics- Nano level techniques- Optical spectroscopy in all its forms. The journal is reluctant to include most drug and strictly clinical studies as there are more suitable publication platforms for these types of papers.