EV Translational Horizons as Viewed Across the Complex Landscape of Liquid Biopsies

Abstract

Extracellular Vesicle (EV)-based diagnostic and therapeutic tools are an area of intensive study and substantial promise, but EVs as liquid biopsies have advanced years ahead of EVs as therapeutic tools. EVs are emerging as a promising approach for detecting tumors, evaluating the molecular profiles of known disease, and monitoring treatment responses. Although correlative assays based on liquid biopsies are already having an impact on translational studies and clinical practice, much remains to be learned before these assays will be optimized for clinical correlations, functional biological studies, and therapeutic use. What follows is an overview of current evidence supporting the investigation and use of liquid biopsies, organized by specific liquid biopsy components available for analysis, along with a summary of what challenges must be overcome before these assays will provide functional biological insights into the pathogenesis and treatment of disease. The same challenges must also be overcome before it will be feasible to measure and monitor the dosing, distribution, pharmacokinetics, and delivery of EV therapeutics and their cargo in complex biofluids where EVs and circulate with and are co-isolated with a number of other nanoscale materials, including lipoproteins (LPPs), ribonucleoprotein complexes (RNPs), and cell free nucleic acids (cfNA).

Identification of small extracellular vesicle protein biomarkers for pediatric Ewing Sarcoma

“…Small extracellular vesicles (sEVs) or exosomes are a new target for liquid biopsy, which is a non-invasive method of identifying disease specific biomarkers in biological fluids such as blood, saliva, urine, cerebrospinal fluid, etc. (Killingsworth et al, 2021). sEVs are small lipid bilayer membrane containing vesicles with a size range of 40-160 nm in diameter (Kalluri and LeBleu, 2020) that are actively secreted by most cell types in the body including cancer cells and stably circulate in the body.…”

Removal and identification of external protein corona members from RBC‐derived extracellular vesicles by surface manipulating antimicrobial peptides

“…They play important roles in intracellular communication, by trafficking cellular contents including proteins, RNA and DNA within their vesicular body, but they also have the advantage of displaying membrane proteins on their external surface (Ko & Naora, 2020 ; Yang et al., 2018 ). Due to this widespread molecular cargo, there is an extreme diagnostic potential in EVs liquid biopsies (Killingsworth et al., 2021 ; Zhou et al., 2020 ). However, recently increasingly growing evidence suggests that EVs, akin to synthetic nanoparticles, are exposed to spontaneously adsorbing “contaminations” from the protein‐rich blood matrix.…”

The promise of small particles: extracellular vesicles as biomarkers in liver pathology

“…Thus, recently numerous studies have investigated the key roles of EVs in driving liver pathogenesis. These small but mighty vesicles are harnessed by liquid biopsy and act as an excellent diagnostic and therapeutic tool against liver diseases (Killingsworth et al., 2021). In this review, we discuss the potential role of EVs in liver pathobiology, underscoring the promising role of EVs as potential disease biomarkers and the current and future directions of EV research.…”