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A novel photocleavable amino-modified graphene for covalent purification of N-glycans from hepatocellular carcinoma patients' serum for potential biomarkers discovery

文献类型: 外文期刊

作者: Chao, Xuyuan 1 ; Yang, Shengjie 1 ; Zhang, Baoying 1 ; Zang, Xin 1 ; Zhang, Jingyi 1 ; Liu, Xizi 2 ; Chen, Lu 1 ; Qi, Lu 1 ; Xue, Xiaofeng 2 ; Hu, Han 2 ; Wang, Xinghe 1 ;

作者机构: 1.Capital Med Univ, Beijing Shijitan Hosp, PhaseClin Trial Ctr 1, Beijing 100038, Peoples R China

2.Chinese Acad Agr Sci, Inst Apicultural Res, 1 Beigou Xiangshan, Beijing 100093, Peoples R China

3.Shandong First Med Univ, Shandong Canc Hosp & Inst, Shandong Acad Med Sci, PhaseClin Trial Ctr 1, Jinan 250117, Peoples R China

关键词: Photocleavable amino graphene; N-Glycans; Human serum; Hepatocellular carcinoma; Cancer biomarker; MALDI-TOF/TOF MS

期刊名称:CANCER NANOTECHNOLOGY ( 影响因子:4.8; 五年影响因子:5.1 )

ISSN: 1868-6958

年卷期: 2025 年 16 卷 1 期

页码:

收录情况: SCI

摘要: Glycosylation alterations have emerged as significant indicators in the landscape of cancer diagnosis, with aberrant N-glycans standing out as potential biomarkers. The existing methods for purifying N-glycans mainly rely on their hydrophilicity, affinity, and size. These methods exhibit relatively weak binding forces and low specificity based on non-covalent interactions. Moreover, the current liquid chromatography-based N-glycan purification and detection techniques must be bettered for clinical settings' rapid diagnostic requirements. Here, we have developed a method involving the covalent binding of graphene modified with photocleavable amino groups to N-glycans in hepatocellular carcinoma (HCC) patients' serum glycoproteins. The N-glycans are identified using MALDI-TOF/TOF MS, catering to the requirements of biological research and the diagnosis of liver cancer disease. Specifically, amino-functionalized graphene is linked with photocleavable groups bearing hydrazide functional group, then undergoes acyl hydrazone covalent reaction with aldehyde groups on the side chains of oxidized monosaccharides to capture the N-glycans. Finally, under UV irradiation at a wavelength of 356 nm for 15 s, the ortho-nitrobenzyl photocleavable groups undergo cleavage, completing the release of captured N-glycans, which are then subjected to MALDI-TOF/TOF MS mass spectrometry for detection. Our findings demonstrate significant differences in the N-glycan profiles between serum samples of liver cancer patients and healthy individuals. These differences are characterized by increased abundance and molecular weight of N-glycans. Through biomarker screening, one N-glycan with an m/z ratio of 1847.01 shows the potential to serve as a diagnostic biomarker for liver cancer (P < 0.05). Our research underscores the potential of photocleavable amino-modified graphene for detecting aberrant N-glycans in HCC patients' serum to elucidate the intricate between aberrant N-glycan alterations and HCC. This research paves the way for developing novel biomarkers, diagnostic strategies, and therapeutic interventions to combat this complex disease.

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