biostudies-literatureBhatta RUnited States Department of Defense | Defense Advanced Research Projects AgencyUnited States Department of Defense | United States Air Force | AFMC | Air Force Office of Scientific ResearchU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of HealthNational Science Foundation8047https://www.ebi.ac.uk/biostudies/studies/S-EPMC10697976biostudies-literatureUnknown14(1)As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8⁺ T cell response. These lead to 80% tumor-free Nature communicationsMetabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines.PMC10697976FA9550-23-1-0609R01 CA274738N660012314013NIH R01CA274738R21 CA270872NIH R21CA270872R01CA234025DMR 2143673 CARLiu YChen QHassaneen WBo YZhang XSHan JWang HBhatta RWang YNelson ERLee DZhou JfalseMetabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines.As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8⁺ T cell response. These lead to 80% tumor-free 2023-01-01T00:00:00Z2023 Dec2025-04-25T17:19:47.336Z2025-04-06T05:13:25.863ZS-EPMC106979763805286910.1038/s41467-023-43914-8