State Key Laboratory for Organic Electronics and Information Displays, Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
State Key Laboratory for Organic Electronics and Information Displays, Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
Biosens Bioelectron. 2025 Jan 1;267:116737. doi: 10.1016/j.bios.2024.116737. Epub 2024 Sep 4.
Exosomes have emerged as a promising noninvasive biomarker for early cancer diagnosis due to their ability to carry specific bioinformation related to cancer cells. However, accurate detection of trace amount of cancer-derived exosomes in complex blood remains a significant challenge. Herein, an ultra-highly sensitive SERS sensor, powered by the branched hybridization chain reaction (bHCR) and tetrahedral DNA-based trivalent aptamer (triApt-TDN), has been proposed for precise detection of cancer-derived exosomes. Taking gastric cancer SGC-7901 cells-derived exosomes as a test model, the triApt-TDNs were constructed by conjugating aptamers specific to mucin 1 (MUC1) protein with tetrahedral DNAs and subsequently immobilized on the surface of silver nanorods (AgNRs) arrays to create SERS-active sensing chips capable of specifically capturing exosomes overexpressing MUC1 proteins. The bHCR was further initiated by the trigger aptamers (tgApts) bound to exosomes, and as a result the SERS tags were assembled into AuNP network structures with abundant SERS hotspots. By optimizing the sensing conditions, the SERS sensor showed good performance in ultra-highly sensitive detection of target exosomes within 60 min detection time, with a broad response ranging of 1.44 to 1.44 × 10 particles·μL and an ultralow limit of detection capable of detecting a single exosome in 2 μL sample. Furthermore, the SERS sensor exhibited good uniformity, repeatability and specificity, and capability to distinguish between gastric cancer (GC) patients and healthy controls (HC) through the detection of exosomes in clinical human serums, indicating its promising clinical potential for early diagnosis of gastric cancer.
外泌体因其能够携带与癌细胞相关的特定生物信息而成为一种很有前途的非侵入性癌症早期诊断生物标志物。然而，在复杂的血液中准确检测痕量的癌症来源外泌体仍然是一个重大挑战。在此，提出了一种基于分支杂交链式反应（bHCR）和四面体 DNA 三价适配体（triApt-TDN）的超灵敏 SERS 传感器，用于精确检测癌症来源的外泌体。以胃癌 SGC-7901 细胞来源的外泌体作为测试模型，通过将特异性结合黏蛋白 1（MUC1）蛋白的适配体与四面体 DNA 偶联，并将其固定在银纳米棒（AgNRs）阵列表面，构建了能够特异性捕获过度表达 MUC1 蛋白的外泌体的 SERS 活性传感芯片。进一步通过与外泌体结合的触发适配体（tgApts）引发 bHCR，结果是 SERS 标记物被组装成具有丰富 SERS 热点的 AuNP 网络结构。通过优化传感条件，该 SERS 传感器在 60 分钟的检测时间内对外泌体的超灵敏检测表现出良好的性能，具有 1.44 至 1.44×10 个粒子·μL 的宽响应范围和能够在 2μL 样品中检测单个外泌体的超低检测限。此外，该 SERS 传感器表现出良好的均匀性、重复性和特异性，并且能够通过检测临床人血清中外泌体来区分胃癌（GC）患者和健康对照（HC），表明其在胃癌早期诊断方面具有有前景的临床应用潜力。
