Intersections of focused ultrasound and extracellular vesicles: Toward diversified biomarker enrichment and discovery

Abstract

Extracellular vesicles (EVs) are heterogeneous, membrane-bound structures shed by most fluid-interfacing cell types and play a critical role in orchestrating pathophysiological processes. With the advancement of liquid biopsy for cancer diagnosis and surveillance, EVs have burgeoned as a powerful asset toward circulating biomarker discovery owing to their diverse cargo (i.e., proteins, metabolites, nucleic acids, lipids). With the advent of focused ultrasound (FUS) technology as a tool for “sonobiopsy” in solid tumors, we recognize the increasing importance of deconvolving how the diverse bioeffects of FUS may influence EV quantity and quality. We have examined the impacts of thermal and mechanical FUS regimens on EV release and profile across cancer and immune cell contexts. Our observations suggest that both hyperthermia and microbubble-assisted FUS augment EV release acutely. On closer examination, hyperthermia-exposed EVs also display shifts in proteomic profile and differential immunomodulatory capacity. Ongoing studies are interrogating the impact of other FUS regimens on EV biology. Meanwhile, we are also directly investigating EVs from liquid biopsy specimens spanning murine cancer models, veterinary oncology (spontaneous canine cancers), and clinical trials. We expect that a continued work at the functional intersection of FUS and EVs will yield important, timely insight for this rapidly evolving field.