Exosome-templated nanoplasmonics for multiparametric molecular profiling

Abstract

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis—through simultaneous biophysical and biomolecular evaluation of the same vesicles—directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

Biomarker Organization in Circulating Extracellular Vesicles: New Applications in Detecting Neurodegenerative Diseases

“…These strategies could be integrated with nanoscale molecular sensing technologies [106,107] to enable sensitive and multiplexed detection of EV cargoes. Further integration with portable and miniaturized devices [33,96] could assist in realizing facile EV detection in point-of-care settings, thereby accelerating large-scale clinical validation studies.…”

“…Current analytical approaches (e.g., Western blotting and ELISA), however, are not only limited in their capacity to differentiate between EV biomarkers and other non-EV molecules in biofluids, but also do not have sufficient structural resolution to distinguish the different organizational states of EV molecular cargoes. [95,96] This limitation could have resulted in the poor performance of current blood-based measurements, wherein blood analyses of ensemble pathological molecules show poor correlation to the brain pathology of patients. [91]…”

Microfluidic‐Based Exosome Analysis for Liquid Biopsy

“…Reproduced with permission. [ 121 ] Copyright 2020, American Association for the Advancement of Science (AAAS).…”

Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

“…Additionally, drug loading and delivery efficiency can be improved through the design of exosome-like nanovesicles and membrane-camouflaged nanoparticles 217 . For example, to combine their biophysical and biomolecular advantages, gold nanoshells (which are non-cytotoxic 218 ) were assembled and grown on vesicles in situ to achieve rapid and multiplexed analysis of exosomal targets, offering a novel avenue for accurate patient prognosis and therapy 219 ( Figure 3 ). In summary, we anticipate that native and bioengineered exosomes will be translated to atherosclerosis management, and we expect that exosome-like nanoparticles will become effective strategies to address current problems.…”