Polymeric hydrophilic ionic liquids used to modify magnetic nanoparticles for the highly selective enrichment of N-linked glycopeptides

The low abundance of glycopeptides in biological samples makes it necessary to enrich them before further analysis. In this study, the polymeric hydrophilic ionic liquid-modified magnetic (Fe₃O₄@MPS@PMAC) nanoparticles were synthesized via a one-step reflux-precipitation polymerization. Owing to the excellent hydrophilicity and strong electrostatic interaction toward glycopeptides of the polymerized hydrophilic ionic liquid, [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MAC), the synthesized Fe₃O₄@MPS@PMAC nanoparticles exhibited outstanding performance in glycopeptide enrichment with high detection sensitivity (10 fmol), large binding capacity (100 μg mg^-1) and satisfied enrichment recovery (approximately 82%). Furthermore, the newly developed Fe₃O₄@MPS@PMAC nanoparticles were applied for the glycopeptide enrichment of HeLa exosome proteins. A total of 1274 glycopeptides from 536 glycoproteins were identified in three replicate analyses of 50 μg of HeLa exosome proteins. These results demonstrate the potential of Fe₃O₄@MPS@PMAC nanoparticles for both glycoproteomic analysis and exosome research.