The extracellular vesicle biomolecular corona: current insights and diagnostic potential

Extracellular vesicles (or EVs) are biogenic nanoparticles released by all cell types, playing a central role in intercellular communication by transporting proteins, nucleic acids, and metabolites. Over the past 5 years, it has become evident that, similarly to synthetic nanoparticles, EVs acquire a dynamic layer of biomolecules from the surrounding biological fluids. These spatially correlated and time-resolved interactions between EVs and the other molecular and nanoscale components of the biological environment are named biomolecular corona, and concur in shaping the biological identity, function, and fate of EVs. In this review, we first outline the physicochemical interactions that drive biomolecular corona formation on EVs and its principal biomolecular components. We then compare ex situ and in situ characterization techniques currently employed to study the EVs and EV corona complexes, highlighting their respective advantages and limitations. Finally, we discuss how advancing our understanding of the EV corona could significantly improve the robustness of EV-based biomarkers and enhance the specificity of liquid biopsy strategies, ultimately contributing to the development of next-generation precision medicine and personalized diagnostics.