Zhang Jingjing, Yan Chenlong, Xie Lijie, Ding Qingzhong, He Xiyu, Liu Jian, Wang Tingxiao, Gu Xinyue, Wang Lianhui, Song Chunyuan
State Key Laboratory of Flexible Electronics (LoFE), Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
State Key Laboratory of Flexible Electronics (LoFE), Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
Biosens Bioelectron. 2025 Aug 15;282:117497. doi: 10.1016/j.bios.2025.117497. Epub 2025 Apr 18.
Exosome-based liquid biopsy plays an increasingly important role in non-invasive cancer diagnosis. However, due to their small size and low abundance, sensitive and accurate detection of cancer-derived exosomes in complex biological samples still faces great challenges. Herein, an ultrasensitive SERS assay based on the multivalent aptamer-linked tetrahedron DNA (MATD) assisted catalytic hairpin assembly (CHA) was developed for accurate detection of cancer-derived exosomes, including MATD-modified SERS sensing chip, identification SERS tags (IS), and assist SERS tags (AS). Taking SGC-7901 cell-derived exosomes as a test model, the exosomes can be captured onto the SERS sensing chip by the specific binding of multivalent aptamers to CD63 proteins, and then the MUC1 aptamers on the IS bind to the highly expressed MUC1 proteins on the SGC-7901 cell-derived exosomes to release the patch strands (P), further triggering the CHA-induced assembly of AuNP network structures between IS and AS with rich hotspots on SERS sensing chip. The proposed SERS assay can achieve ultra-high sensitivity low to 2.98 × 10 particles mL (i.e., approximately 6 exosome particles can be detected from 2 μL of biological sample) within 40 min, high specificity for identifying SGC-7901 cell-derived exosomes, and can accurately distinguish gastric cancer patients from healthy people, which shows the potential applications in clinical diagnosis.
基于外泌体的液体活检在非侵入性癌症诊断中发挥着越来越重要的作用。然而，由于其尺寸小、丰度低，在复杂生物样品中灵敏且准确地检测癌症来源的外泌体仍然面临巨大挑战。在此，我们开发了一种基于多价适配体连接四面体DNA（MATD）辅助催化发夹组装（CHA）的超灵敏表面增强拉曼光谱（SERS）检测方法，用于准确检测癌症来源的外泌体，包括MATD修饰的SERS传感芯片、识别SERS标签（IS）和辅助SERS标签（AS）。以SGC-7901细胞来源的外泌体作为测试模型，外泌体可通过多价适配体与CD63蛋白的特异性结合被捕获到SERS传感芯片上，然后IS上的MUC1适配体与SGC-7901细胞来源外泌体上高表达的MUC1蛋白结合，释放出补丁链（P），进一步触发CHA诱导IS和AS之间在SERS传感芯片上形成具有丰富热点的金纳米颗粒网络结构。所提出的SERS检测方法能够在40分钟内实现低至2.98×10颗粒/毫升的超高灵敏度（即从2微升生物样品中可检测到约6个外泌体颗粒），对识别SGC-7901细胞来源外泌体具有高特异性，并且能够准确区分胃癌患者和健康人，这显示了其在临床诊断中的潜在应用价值。
