Investigation of rare earth-based magnetic nanocomposites for specific enrichment of exosomes from human plasma

Exosomes, also known as small extracellular vesicles, are widely present in a variety of body fluids (e.g., blood, urine, and saliva). Exosomes are becoming an alternative promising source of diagnostic markers for disease rich in cargo of metabolites, proteins, and nucleic acids. However, due to the low abundance and structure similarity with protein complex, the efficient isolation of exosomes is one of the most important issues for biomedical applications. With a higher order of f-orbitals in rare earth element, it will have strong adsorption toward the phosphate group on the surface of the phospholipid bilayer of exosomes. In this study, we systematically investigated the ability of various rare earths interacting with phosphate-containing molecules and plasma exosomes. One of the best binding europium was selected and used to synthesize core-shell magnetic nanomaterials (Fe3O4@SiO2@Eu2O3) for the enrichment of exosomes from human plasma. The developed nanomaterials exhibited higher enrichment capacity, less time consumption and more convenient handling compared to commonly used ultracentrifugation method. The nanomaterials were applied to separate exosomes from the plasma of patients with hepatocellular carcinoma and healthy controls for metabolomics study with high-resolution mass spectrometry, where 70 differentially expressed metabolites were identified, involving amino acid and lipid metabolic pathway. We anticipated the rare earth-based materials to be an alternative approach on exosome isolation for disease diagnosis or postoperative clinical monitoring.