Porous composite materials driven by carbohydrate-carbohydrate interactions for efficient enrichment of intact...

Aberrant N-glycosylation plays a key role in liver cancer progression, making glycopeptides promising biomarker candidates. With the increasing awareness of the potential for novel types and features of glycopeptides, there is a pressing need for advanced enrichment materials to facilitate their sensitive and specific detection. Here, we report the development of a hydrophilic material (DMSN-CS-LA) based on carbohydrate-carbohydrate interactions (CCI), which involves coating chitosan-lactobionic acid (CS-LA) onto the surface of dendritic mesoporous silica. DMSN-CS-LA exhibited outstanding performance in glycopeptide enrichment, with a low detection limit (2 fmol/μL), remarkable identification selectivity (IgG:BSA = 1:500), and an ideal loading capacity (300 mg/g). Significantly, this study reports the first application of a solid-phase enrichment material to hepatocellular carcinoma using the SMMC-7721 cell line. The results showed that 455 N-glycopeptides corresponding to 187 glycoproteins were enriched from 150 μg SMMC-7721 cell digests. Gene Ontology (GO) analysis linked the enriched N-glycopeptides to liver cancer development. Simultaneous capture of biomarkers including Lamin-B1, Transferrin receptor protein 1, Fatty acid-binding protein 5, folate receptor 1, and Aminopeptidase N, underscores the method's potential for early diagnosis and prognosis. Overall, DMSN-CS-LA offers an effective enrichment platform, advancing glycoproteomic analysis in cancer research.