Ultra-hydrophilic MXene nanoplatform unraveling plasma N-glycopeptide in epidural-related maternal fever.

Given the high incidence of epidural‑related maternal fever (ERMF) among women with epidural analgesia and the key roles of glycoproteins, an efficient nanoplatform is needed for N‑glycoproteomic analysis to better understand ERMF. Herein, we constructed an ultra-hydrophilic magnetic MXene-based nanoplatform (MMX-Cys) for efficient N-glycopeptide enrichment. By integrating the high surface area of MXene, the hydrophilicity of L-cysteine, MMX-Cys demonstrated ultra-hydrophilicity with a water contact angle of ~ 0°. It exhibits high sensitivity (1 fmol·µL⁻¹), excellent selectivity (HRP: BSA = 1:100), and good reproducibility in enriching glycopeptides from standard protein digests. Applied to plasma samples from ERMF patients and healthy controls, the MMX-Cys based nanoplatform enabled the identification of 1195 N-glycopeptides corresponding to 91 glycoproteins. Differential expression analysis revealed 18 significantly altered glycopeptides from 10 glycoproteins, predominantly involved in humoral immunity and complement activation, including immunoglobulin heavy chains (IGHG1, IGHG2, IGHA1, IGHA2) and complement component C2. This study presents an effective tool for N-glycopeptide determination and provides glycoproteomic evidence supporting the inflammatory pathogenesis of ERMF. The MMX-Cys based nanoplatform holds great potential in offering a foundation for future biomarker discovery and mechanistic studies.