Nanoplasmonic quantification of tumour-derived extracellular vesicles in plasma microsamples for diagnosis and treatment monitoring

• Published in: Nature biomedical engineering Vol. 1; no. 4
• Main Authors: Liang, Kai, Liu, Fei, Fan, Jia, Sun, Dali, Liu, Chang, Lyon, Christopher J., Bernard, David W., Li, Yan, Yokoi, Kenji, Katz, Matthew H., Koay, Eugene J., Zhao, Zhen, Hu, Ye
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2017; Nature Publishing Group
• Subjects: 631/61/32; 692/53/2421; Antibodies; Assaying; Biomarkers; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Blood plasma; Cancer; Diagnosis; Diagnostic systems; Enzyme-linked immunosorbent assay; EphA2 protein; Extracellular vesicles; Monitoring; Nanoparticles; Nanorods; Nanospheres; Pancreatic cancer; Pancreatitis; Patients; Telemedicine; Tumors; Vesicles
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-016-0021

Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples and are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumour-derived EVs from as little as 1 μl of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity. We identified a pancreatic cancer EV biomarker, ephrin type-A receptor 2 (EphA2), and demonstrate that an nPES assay for EphA2-EVs distinguishes pancreatic cancer patients from pancreatitis patients and healthy subjects. EphA2-EVs were also informative in staging tumour progression and in detecting early responses to neoadjuvant therapy, with better performance than a conventional enzyme-linked immunosorbent assay. The nPES assay can be easily refined for clinical use, and readily adapted for diagnosis and monitoring of other conditions with disease-specific EV biomarkers. A rapid, inexpensive and ultrasensitive assay that uses antibody-conjugated nanoparticle probes on the surface of a sensor chip quantifies tumour-derived extracellular vesicles to detect pancreatic cancer from 1 μl of blood plasma.