Biomolecular Corona of Extracellular Vesicles: Report on Isev Workshop.

The concept of the "biomolecular corona" (BC) was first introduced to describe the spontaneous absorption of molecules, mainly proteins, onto the surface of synthetic nanoparticles upon exposure to biological fluids. More recently, the same term has been used to describe biomolecules that dynamically interact with the surface of extracellular vesicles (EVs) during their biogenesis, secretion, or upon exposure to intracellular or extracellular milieus, including biological fluids. The EV biomolecular corona is a key determinant of EV identity, shaping their cellular uptake, biodistribution, and functional outcomes in both physiological and pathological contexts. EVs, in contrast to synthetic nanoparticles, introduce distinct challenges and perspectives due to their biological origin, innate heterogeneity, and complex combination of physicochemical and biological properties. To address this evolving topic, the International Society for Extracellular Vesicles (ISEV) organized a dedicated workshop in Brescia, Italy, on 27th to 28th February, 2025. The event gathered selected participants from academia and industry, with expertise spanning synthetic nanomaterials, EVs, biophysics, and translational nanomedicine. The program included keynote lectures, oral presentations, posters, and a series of interactive roundtables structured around fundamentals of the biomolecular corona, EV corona biogenesis and composition, analytical and separation tools and clinical and diagnostic potential applications. This report summarizes the key scientific insights, methodological challenges, conceptual debates, and future perspectives that emerged from the workshop.