Targeted Imaging and Proteomic Analysis of Tumor-Associated Glycans in Living Animals

• Published in: Angewandte Chemie International Edition Vol. 53; no. 51; pp. 14082 - 14086
• Main Authors: Xie, Ran, Dong, Lu, Huang, Rongbing, Hong, Senlian, Lei, Ruoxing, Chen, Xing
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 15.12.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Animals; Azides - chemistry; Cancer; click chemistry; Encapsulating; Fluorescence; Fluorescent Dyes - chemistry; Glycan; Glycoproteins; Glycoproteins - analysis; Imaging; integrin ligands; Ligands; liposomes; Liposomes - chemistry; Marking; Mathematical models; Melanoma; Melanoma - chemistry; Melanoma - pathology; Mice; Nanoparticles - chemistry; Neoplasms, Experimental - chemistry; Oligosaccharides - chemistry; Proteomics; Rodents; sialic acids; Strategy; tumor imaging; Tumors; click chemistry; sialic acids; tumor imaging; liposomes; integrin ligands
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201408442

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. Sweet target: A strategy for the targeted imaging of tumor‐associated glycans is reported and makes use of ligand‐targeted liposomes encapsulating azidosugars. The azidosugars were selectively incorporated into the melanoma glycans in a xenograft mouse model and were then reacted with fluorophores by using copper‐free click chemistry for in vivo imaging or with affinity tags for proteomic analysis.