title: Targeted imaging and proteomic analysis of tumor-associated glycans in living animals.
abstract: Although it has been well known that dynamic changes in glycosylation are associated with tumor progression, it remains challenging to selectively visualize the cancer glycome in vivo. Herein, a strategy for the targeted imaging of tumor-associated glycans by using ligand-targeted liposomes encapsulating azidosugars is described. The intravenously injected liposomal nanoparticles selectively bound to the cancer-cell-specific receptors and installed azides into the melanoma glycans in a xenograft mouse model in a tissue-specific manner. Subsequently, a copper-free click reaction was performed in vivo to chemoselectively conjugate the azides with a near-infrared fluorescent dye. The glycosylation dynamics during tumor growth were monitored by in vivo fluorescence imaging. Furthermore, the newly synthesized sialylated glycoproteins were enriched during tumor growth and identified by glycoproteomics. Compared with the labeling methods using free azidosugars, this method offers improved labeling efficiency and high specificity and should facilitate the elucidation of the functional role of glycans in cancer biology.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871 (P.R. China).
authors.forename: Ran
authors.initials: R
authors.lastname: Xie
authors.forename: Lu
authors.initials: L
authors.lastname: Dong
authors.forename: Rongbing
authors.initials: R
authors.lastname: Huang
authors.forename: Senlian
authors.initials: S
authors.lastname: Hong
authors.forename: Ruoxing
authors.initials: R
authors.lastname: Lei
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001386:Azides / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006023:Glycoproteins / Q000032:analysis*; D008024:Ligands; D008081:Liposomes / Q000737:chemistry; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry*; D040901:Proteomics
chemical_list: D001386:Azides; D005456:Fluorescent Dyes; D006023:Glycoproteins; D008024:Ligands; D008081:Liposomes; D009844:Oligosaccharides
keywords: click chemistry; integrin ligands; liposomes; sialic acids; tumor imaging