Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Biomater Sci. 2019 Oct 1;7(10):4166-4173. doi: 10.1039/c9bm00898e. Epub 2019 Aug 1.
Metabolic glycoengineering of unnatural monosaccharides provides a facile method to label cancer cells with chemical tags for glycan imaging and cancer targeting. Multiple types of monosaccharides have been utilized for metabolic cell labeling. However, the comparison of different types of monosaccharides in labeling efficiency and selectivity has not been reported. In this study, we compared N-azidoacetylgalactosamine (GalAz) and N-azidoacetylmannosamine (ManAz) for metabolic labeling of HepG2 hepatocellular carcinoma in vitro and in vivo. GalAz showed higher labeling efficiency at low concentrations, and outperformed ManAz in metabolic labeling of HepG2 tumors in vivo. GalAz mediated labeling of HepG2 tumors with azido groups significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)-Cy5 and DBCO-doxorubicin conjugate via efficient Click chemistry. This study, for the first time, uncovered the distinct labeling efficiency and selectivity of different unnatural monosaccharides in liver cancers.
非天然单糖的代谢糖基工程为用化学标记物标记癌细胞进行聚糖成像和癌症靶向提供了一种简便的方法。已经使用多种类型的单糖进行了代谢细胞标记。然而，不同类型的单糖在标记效率和选择性方面的比较尚未报道。在这项研究中，我们比较了 N-叠氮乙酰半乳糖胺（GalAz）和 N-叠氮乙酰甘露糖胺（ManAz）在体外和体内代谢标记 HepG2 肝癌细胞的效率。GalAz 在低浓度下显示出更高的标记效率，并且在体内代谢标记 HepG2 肿瘤方面优于 ManAz。GalAz 介导的叠氮基团对 HepG2 肿瘤的标记显著提高了二苯并环辛炔（DBCO）-Cy5 和 DBCO-阿霉素缀合物通过有效的点击化学的肿瘤积累。这项研究首次揭示了不同非天然单糖在肝癌中的独特标记效率和选择性。
