Journal
NATURE BIOMEDICAL ENGINEERING
Volume 1, Issue 4, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41551-016-0021
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Funding
- NIH [R01AI113725, R01AI122932, U54CA143837, 5P50CA126752-08]
- NIH intramural research program
- John S. Dunn Foundation award
- PANCAN-AACR Career Development Award [14-20-25-KOAY]
- Radiological Society of North America seed grant [RSD1429]
- Sheikh Ahmed Center for Pancreatic Cancer Research at The University of Texas M.D. Anderson Cancer Center
- Center for Radiation Oncology Research at The University of Texas M.D. Anderson Cancer Center
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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 mu l 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.
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