One-step fabrication of strongly hydrophilic mesoporous silica for comprehensive analysis of serum glycopeptidome

Glycopeptidome represents reliable predictors of physiological and pathological status. Obstructions mainly including low abundance of endogenous glycopeptides and varied interference necessitate glycopeptide enrichment prior to MS analysis. Inspired by the prevalence of hydrophilic interaction chromatography for glycopeptide enrichment, a novel magnetic mesoporous silica nanomaterial (Fe3O4@mSiO2-TSG) with strongly hydrophilic property was developed through a one-pot method. In this work, the gluconamide-containing organosilane is innovatively proposed to directly serve as the strongly hydrophilic silica source for fabrication of hydrophilic mesoporous silica nanomaterial for glycopeptidomics research. Apart from excellent hydrophilicity, Fe3O4@mSiO2-TSG also was equipped with large specific surface area, ordered mesopore channels and great magnetic responsiveness. With all the advantages, Fe3O4@mSiO2-TSG displayed remarkable size-exclusion effect and considerable reusability. Moreover, combined with nano-LC-MS/MS, the glycopeptidome of serum from breast cancer patients was analyzed comprehensively, which showed noteworthy difference from healthy serum through gene ontology analysis, indicating great potential of the approach for glycopeptidomics research. A strongly hydrophilic mesoporous silica nanomaterial denoted as Fe3O4@mSiO2-TSG was prepared through one-pot synthetic method, and applied in glycopeptide identification from human serum. [Display omitted] •A novel hydrophilic mesoporous silica was designed via one-step synthesis method.•Fe3O4@mSiO2-TSG exhibited remarkable size-exclusion effect for glycopeptide capture.•Disease-related serum endogenous glycopeptidome research was discussed.