Abstract
All cells release a multitude of nanoscale extracellular vesicles (nEVs) into circulation, offering immense potential for new diagnostic strategies. Yet, clinical translation for nEVs remains a challenge due to their vast heterogeneity, our insufficient ability to isolate subpopulations, and the low frequency of disease-associated nEVs in biofluids. The growing field of nanoplasmonics is poised to address many of these challenges. Innovative materials engineering approaches based on exploiting nanoplasmonic phenomena, i.e., the unique interaction of light with nanoscale metallic materials, can achieve unrivaled sensitivity, offering real-time analysis and new modes of medical and biological imaging. We begin with an introduction into the basic structure and function of nEVs before critically reviewing recent studies utilizing nanoplasmonic platforms to detect and characterize nEVs. For the major techniques considered, surface plasmon resonance (SPR), localized SPR, and surface enhanced Raman spectroscopy (SERS), we introduce and summarize the background theory before reviewing the studies applied to nEVs. Along the way, we consider notable aspects, limitations, and considerations needed to apply plasmonic technologies to nEV detection and analysis.
Highlights
Nanoscale extracellular vesicles encompass a heterogeneous grouping of naturally occurring nanoparticles that are endogenously secreted by all cells tested to date (Mathieu et al, 2019)
For the major techniques considered, surface plasmon resonance (SPR), localized SPR, and surface enhanced Raman spectroscopy (SERS), we introduce and summarize the background theory before reviewing the studies applied to Nanoscale extracellular vesicles (nEVs)
These technologies may offer significant insight into nEV structure, function, and behavior, as (i) their size does not require ground-breaking sensitivity to observe single binding or sensing events (Zeng et al, 2019), (ii) most nanoplasmonic setups are realized as optical imaging platforms that can be integrated with fluorescence microscopy for increased multiplexing or direct imaging, (iii) the rapid timescale of plasmonic phenomena, combined with ongoing technical improvements allow for realtime tracking of nEV motion and interactions, and (iv) labelingapproaches where nanoplasmonic materials are bound to targeted extracellular vesicles (EVs) subpopulations may have the advantage of subdiffraction imaging, effectively increasing spatial resolution (Hermann and Gordon, 2018)
Summary
Nanoscale extracellular vesicles (nEVs) encompass a heterogeneous grouping of naturally occurring nanoparticles that are endogenously secreted by all cells tested to date (Mathieu et al, 2019). No category of techniques may have more promise than nanoplasmonics, the field of engineering nanoscale metallic surfaces for the significant enhancement of analytical signals, both in magnitude and in terms of molecular specificity. Nanoplasmonic innovations are difficult to translate into clinical diagnostic platforms due to both the inherent complexity of the techniques themselves, and as a result of the compositional and temporal heterogeneity of biological agents inside the human body during disease progression. Such heterogeneity is a particular hallmark of nEVs (Tkach et al, 2018)
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