Multiple Exposures of Plasma to Nanoparticles: A Novel Tool to Personalize Biomolecular Coronas and Fractionate Fluids

Nanoparticles (NPs) have emerged as a valuable tool for biomarker discovery due to their ability to interact with biological fluids and form biomolecular coronas. In this study, we introduce a multiple exposure method that uses NPs to fractionate biological fluids and obtain personalized coronas. By repeatedly exposing plasma to silica NPs, we observed a progressive change of the biomolecule profile in both the pellet and supernatant. The varying protein and glycan composition of the corona was characterized using techniques such as SDS-PAGE, mass spectrometry, and UHPLC. Notably, the corona's composition evolved with each exposure cycle, reflecting the selective binding of proteins and glycosylated molecules from a corona of high-affinity biomolecules to a more diverse corona with very distinct structures. By tracing the sequential modification of protein and glycan composition, we believe that the method can be useful to trace specific biomarker profiles, offering a noninvasive alternative to conventional diagnostic processes with the potential to become a useful tool for disease monitoring and advanced biomedical applications.