Supplementary file 1_Small extracellular vesicle-associated surface protein biomarkers: emerging roles, opportunities, and challenges in diagnostics.docx

Investigation into the use of small extracellular vesicles (sEVs) or the specific subtype exosomes as diagnostic markers has been growing in both research output and market potential, especially in recent years. Despite these ongoing efforts, there is a lack of understanding of the value of sEV surface protein biomarkers beyond just generic tetraspanins as detected analytes in liquid biopsy. While sEV-encapsulated biomolecules, such as nucleic acids or soluble proteins, have been rigorously studied, dependence on sEV lysis would compromise the sensing robustness and diagnostic efficiency. This review article provides a comprehensive overview of sEV transmembrane proteomic signatures and highlights state-of-the-art sensors aiming towards the goal of early diagnosis and clinical monitoring of disease-associated exosomal surface protein markers.

近年来，以小细胞外囊泡（small extracellular vesicles, sEVs）及其特定亚型外泌体（exosomes）作为诊断标志物的相关研究，无论研究产出还是市场潜力均持续攀升。尽管相关研究持续推进，但学界对液体活检（liquid biopsy）中作为检测分析物的小细胞外囊泡表面蛋白生物标志物的认知仍仅局限于通用型四次跨膜蛋白（tetraspanins），对其实际应用价值的理解尚存不足。虽然针对小细胞外囊泡包载的生物分子（如核酸或可溶性蛋白）已有大量深入研究，但依赖小细胞外囊泡裂解的检测手段会削弱传感稳定性与诊断效能。本综述全面梳理了小细胞外囊泡跨膜蛋白质组特征，并重点介绍了当前最先进的传感技术，旨在实现疾病相关外泌体表面蛋白标志物的早期诊断与临床监测。