Haofei Hong, Yanchun Li, Dan Li, Han Lin, Jie Zhao, Zheng Wang, Zhimeng Wu
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Tumor Cell-Specific Metabolic Labelling of Surface Sialoglycans and Post-Click with Multivalent Rhamnose Enable Precise Immune Killing by Endogenous Antibody
We report the design and development of a β-glucuronidase (β-Glu)-responsive ManNAz derivative, Glu-AAM, for tumor-selective metabolic glycoengineering. Glu-AAM enables specific labeling of tumor cell surface sialoglycans in the presence of overexpressed β-Glu in cancer cells, including breast, leukemia, and colorectal cancer cells. We demonstrate the high selectivity and efficiency of Glu-AAM-mediated metabolic glycoengineering across multiple cancer cell lines. Furthermore, we synthesized multivalent antibody-recruiting molecules (DBCO-Rha) that can be covalently attached to the azido-modified tumor cell surface, leading to potent antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity. The octameric DBCO-Rha8 construct exhibited the most effective immune response. This integrated strategy of β-Glu-responsive metabolic glycoengineering and antibody-recruiting immunotherapy provides a promising platform for targeted cancer therapies and expands the toolbox of metabolic glycoengineering for cancer immunotherapy.
期刊介绍：
The Chinese Journal of Chemistry is an international forum for peer-reviewed original research results in all fields of chemistry. Founded in 1983 under the name Acta Chimica Sinica English Edition and renamed in 1990 as Chinese Journal of Chemistry, the journal publishes a stimulating mixture of Accounts, Full Papers, Notes and Communications in English.
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