Synthesis and functionalization of magnetic nanoparticles for glycoprotein and glycopeptide enrichment: A review

Significant progress in the development of magnetic nanoparticles (MNPs) as enrichment platforms of glycosylated biomolecules has been achieved in the past decade due to its remarkable physicochemical properties. The surface of nanomaterials can undergo modification with diverse functional groups which facilitate sensitive and specific interactions with the carbohydrate-based moieties of glycoproteins and glycopeptides. The multimodal capability of MNPs, coupled with their high magnetic susceptibility, offers a rapid, robust, and cost-efficient platform in pre-concentrating and separating glycopeptides with non-glycopeptides prior to mass spectrometry (MS) analysis. This review explores recent progresses, emerging trends, and fundamental principles in synthesizing and functionalizing MNPs for glycoprotein and glycopeptide separation. Physicochemical considerations of MNPs that impact enrichment efficiency (i.e., size, monodispersity, solubility, and surface functionalization) are highlighted. We compare the advantages and disadvantages of various chemical-based approaches to MNP synthesis, with particular emphasis on how reaction parameters influence their physicochemical properties. The review focuses on the underpinning interaction modes (i.e., hydrophilic interaction liquid chromatography, lectin affinity, covalent bond formation, and chelation chemistry) between MNPs and biomolecules which are regulated by the functional groups in the material surface. Finally, we outline design principles and offer future perspectives aimed at enhancing the efficacy of MNPs in glycoproteome enrichment applications.