National Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Anal Chem. 2024 May 14;96(19):7651-7660. doi: 10.1021/acs.analchem.4c00558. Epub 2024 May 1.
Development of molecular diagnostics for lung cancer stratification and monitoring is crucial for the rational planning and timely adjustment of treatments to improve clinical outcomes. In this regard, we propose a nanocavity architecture to sensitively profile the protein signature on small extracellular vesicles (sEVs) to enable accurate, noninvasive staging and treatment monitoring of lung cancer. The nanocavity architecture is formed by molecular recognition through the binding of sEVs with the nanobox-based core-shell surface-enhanced Raman scattering (SERS) barcodes and mirrorlike, asymmetric gold microelectrodes. By imposing an alternating current on the gold microelectrodes, a nanofluidic shear force was stimulated that supported the binding of sEVs and the efficient assembly of the nanoboxes. The binding of sEVs further induced a nanocavity between the nanobox and the gold microelectrode that significantly amplified the electromagnetic field to enable the simultaneous enhancement of Raman signals from four SERS barcodes and generate patient-specific molecular sEV signatures. Importantly, evaluated on a cohort of clinical samples ( = 76) on the nanocavity architecture, the acquired patient-specific sEV molecular signatures achieved accurate identification, stratification, and treatment monitoring of lung cancer patients, highlighting its potential for transition to clinical utility.
开发用于肺癌分层和监测的分子诊断技术对于合理规划和及时调整治疗方案以改善临床结果至关重要。在这方面，我们提出了一种纳米腔结构，用于敏感地分析小细胞外囊泡（sEVs）上的蛋白质特征，从而能够对肺癌进行准确、无创的分期和治疗监测。纳米腔结构通过 sEVs 与基于纳米盒的核壳表面增强拉曼散射（SERS）条码和镜像、非对称金微电极的结合形成分子识别。通过在金微电极上施加交流电，刺激纳米流体剪切力，从而支持 sEVs 的结合和纳米盒的有效组装。sEVs 的结合进一步在纳米盒和金微电极之间诱导纳米腔，显著放大电磁场，从而能够同时增强来自四个 SERS 条码的拉曼信号，并产生患者特异性的分子 sEV 特征。重要的是，在纳米腔结构上对 76 例临床样本的队列进行评估，获得的患者特异性 sEV 分子特征能够准确识别、分层和监测肺癌患者，突出了其向临床应用转化的潜力。
