Tumor Cell-Specific Metabolic Labelling of Surface Sialoglycans and Post-Click with Multivalent Rhamnose Enable Precise Immune Killing by Endogenous Antibody  

作　　者：Haofei Hong Yanchun Li Dan Li Han Lin Jie Zhao Zheng Wang Zhimeng Wu 

机构地区：[1]Key Laboratory of Carbohydrate Chemistry&Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi,Jiangsu,214122 China

出　　处：《Chinese Journal of Chemistry》2025年第1期46-52,共7页中国化学(英文版)

基　　金：supported by the National Natural Science Foundation of China(No.22177040);partly funded by the Fundamental Research Funds for the Central Universities(No.JUSRP123037);the 111 Project(No.111-2-06).

摘　　要：We report the design and development of aβ-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 overexpressedβ-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 ofβ-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.

关 键 词：Metabolic glycoengineering Β-GLUCURONIDASE Antibody recruitment Multivalent rhamnose Cancer immunotherapy Bioimaging CLICKCHEMISTRY Carbohydrates 

分 类 号：R730.5[医药卫生—肿瘤]