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

Abstract

Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples, 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 tumor-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.

Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation

“…These new techniques include nanoscale flow cytometry 43 and integrated nanotechnique-based strategies for biomarkers discovery, using nanoplasmon-enhanced scattering assay. 44 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 detection of a specific subset of EVs. 44 …”

“…44 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 detection of a specific subset of EVs. 44 …”

Novel nanosensing technologies for exosome detection and profiling

“…Besides the platforms reviewed here, many biosensors are being developed to facilitate exosome preparation and analyses 24,27,37,52–55 (Table 1). Such technology development will help deepening our understanding of exosome biology as well as assessing exosomes' clinical value.…”

“…More recent studies have applied novel nanomaterials (e.g. graphene oxide 23 nanorod particles 24 ) or microfluidic analytical systems 25–27 to detect exosomes and identify their protein contents. Development and advancement of such diverse, ultrasensitive detection technologies could offer additional insight into understanding the heterogeneity and production dynamics of exosomes and other EV subtypes.…”

Targeting Tumor‐Associated Exosomes with Integrin‐Binding Peptides

“…It also employs a microfluidic flow system enabling measurements under steady state or dynamic flow conditions, and thus is considered more relevant for characterizing physicochemical phenomena in biological environments. Furthermore, at their best, plasmonic-based measurements offer at least an order of magnitude in increased detection sensitivity compared to ELISA or fluorescence based detection methods, [49] therefore will be an excellent direction to explore in future studies examining binding to clinical samples.…”