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基于肽的生物传感方法用于靶向乳腺癌来源的外泌体。

Peptide-based biosensing approaches for targeting breast cancer-derived exosomes.

机构信息

Biosensing and Bioanalysis Group, Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Spain; Grup de Sensors i Biosensors, Departament de Química, Universitat Autònoma de Barcelona, Bellaterra, Spain; Institute of Chemistry, State University of São Paulo (UNESP), Brazil.

Biosensing and Bioanalysis Group, Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Spain; Grup de Sensors i Biosensors, Departament de Química, Universitat Autònoma de Barcelona, Bellaterra, Spain.

出版信息

Biosens Bioelectron. 2024 Jul 1;255:116211. doi: 10.1016/j.bios.2024.116211. Epub 2024 Mar 19.

Abstract

Exosomes are nanovesicles present in all the biological fluids, making them attractive as non-invasive biomarkers for diseases like cancer, among many others. However, exosomes are complex to separate and detect, requiring comprehensive molecular characterization for their routine use in diagnostics. This study explores the use of peptides as cost-effective and stable alternatives to antibodies for exosome binding. To achieve that, phage display technology was employed to select peptides with high specificity for target molecules in exosomes. Specifically, a selected peptide was evaluated for its ability to selectively bind breast cancer-derived exosomes. Proteomic analysis identified 38 protein candidates targeted by the peptide on exosome membranes. The binding of the peptide to breast cancer-derived exosomes was successfully demonstrated by flow cytometry and magneto-actuated immunoassays. Furthermore, an electrochemical biosensor was also tested for breast cancer-derived exosome detection and quantification. The peptide demonstrated effective binding to exosomes from aggressive cancer cell lines, offering promising results in terms of specificity and recovery. This research shows potential for developing rapid, accessible diagnostic tools for breast cancer, especially in low-resource healthcare settings.

摘要

外泌体存在于所有生物体液中,因此它们作为癌症等疾病的非侵入性生物标志物具有吸引力。然而,外泌体的分离和检测较为复杂,需要进行全面的分子特征分析,才能将其常规应用于诊断。本研究探讨了使用肽作为替代抗体的经济且稳定的选择,用于外泌体结合。为实现这一目标,采用噬菌体展示技术筛选对外泌体中靶分子具有高特异性的肽。具体来说,评估了一种选定的肽选择性结合乳腺癌来源的外泌体的能力。蛋白质组学分析鉴定了外泌体膜上该肽靶向的 38 种候选蛋白。通过流式细胞术和磁驱动免疫测定成功证明了该肽与乳腺癌来源的外泌体的结合。此外,还测试了电化学生物传感器用于检测和定量乳腺癌来源的外泌体。该肽能够有效结合侵袭性癌细胞系来源的外泌体,在特异性和回收率方面具有良好的效果。这项研究为开发快速、易于获取的乳腺癌诊断工具展示了潜力,尤其是在资源有限的医疗环境中。

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