Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.
Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.
Talanta. 2020 Mar 1;209:120557. doi: 10.1016/j.talanta.2019.120557. Epub 2019 Nov 13.
Profile the spatial distributions of endogenous metabolites in heterogeneous tissues is critical to elucidate the complex metabolic mechanisms during pathological progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a label-free technique for tissue imaging that allows simultaneous localisation and quantification of metabolites in different histological regions of interest. In the present study, 1,1'-binaphthyl-2,2'-diamine (BNDM) was developed as a novel MALDI matrix for the detection and imaging of metabolites because of its low background interference, high sensitivity, and applicability in both positive and negative ion modes. 301 negative metabolite ions and 175 positive metabolite ions, including amino acids, organic acids, nucleosides, nucleotides, nitrogenous bases, cholesterols, peptides, fatty acids, cholines, carnitines, polyamines, creatine, phospholipids, etc., were imaged in rat brain when BDMN was used as matrix. Furthermore, BNDM-assisted MALDI-MSI of mouse lung cancer tissue successfully characterized the spatial features of numerous metabolites in viable, necrotic, and connective tissue areas. Importantly, our results demonstrate that the viable area of lung cancer tissue contained a higher abundance of K adducts, while the necrotic area showed a stronger Na adducts intensity. Data-driven segmentation analysis based on the in situ tissue metabolic fingerprints clearly visualized the underlying metabolic heterogeneity of lung cancer, which may provide new insights into the profiling of tumor microenvironment. All these results suggest that the newly developed matrix has great potential application in the field of biomedical research.
描绘不均匀组织中内源性代谢物的空间分布对于阐明病理进展过程中的复杂代谢机制至关重要。基质辅助激光解吸/电离质谱成像（MALDI-MSI）是一种用于组织成像的无标记技术，可在不同感兴趣的组织学区域同时定位和定量代谢物。在本研究中，1,1'-联萘-2,2'-二胺（BNDM）被开发为一种新型 MALDI 基质，用于检测和成像代谢物，因为它具有背景干扰低、灵敏度高以及适用于正离子和负离子模式的特点。当使用 BDMN 作为基质时，在大鼠脑中可以成像 301 个负代谢物离子和 175 个正代谢物离子，包括氨基酸、有机酸、核苷、核苷酸、含氮碱基、胆固醇、肽、脂肪酸、胆碱、肉碱、多胺、肌酸、磷脂等。此外，BNDM 辅助 MALDI-MSI 分析成功地对小鼠肺癌组织中大量代谢物的空间特征进行了表征。重要的是，我们的结果表明，肺癌组织的存活区域含有更高丰度的 K 加合物，而坏死区域则显示出更强的 Na 加合物强度。基于原位组织代谢指纹的数据分析表明，基于数据驱动的分割分析可以清楚地可视化肺癌的潜在代谢异质性，这可能为肿瘤微环境的分析提供新的见解。所有这些结果表明，新开发的基质在生物医学研究领域具有很大的应用潜力。
