Assessing the biomolecular landscape and dynamics of systemically circulating lipid-carrying particles

Separating lipid-carrying particles from body fluids is challenging and complicates studies of extracellular vesicles (EV) and lipoprotein particles (LPP) as disease biomarkers. In this study, we assess the biomolecular composition and dynamics of systemically circulating matched EV and LPP by analyzing serial blood plasma samples from breast cancer, ovarian cancer and HIV patients (n=36). Particles were separated through combined size-exclusion chromatography (SEC) and equilibrium density gradient centrifugation. After the analytical validity of our method is demonstrated, we reveal that EV carry a unique, dynamic and condition-dependent protein composition and RNA profile, which is not directly measurable in LPP extracts and total blood plasma, respectively. Our study extends the knowledge on the compositional nature of the EV protein corona and provides a catalog of proteins associated with systemically circulating EV and LPP. We anticipate that this research will steer the further development of EV-based biomarkers to detect and monitor disease.