TY - JOUR
T1 - Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines
AU - Bhatta, Rimsha
AU - Han, Joonsu
AU - Liu, Yusheng
AU - Bo, Yang
AU - Lee, David
AU - Zhou, Jiadiao
AU - Wang, Yueji
AU - Nelson, Erik Russell
AU - Chen, Qian
AU - Zhang, Xiaojia Shelly
AU - Hassaneen, Wael
AU - Wang, Hua
N1 - H.W. acknowledges the financial support from NSF DMR 2143673 CAR, NIH R01CA274738, NIH R21CA270872, and the start-up package from the Department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign and the Cancer Center at Illinois. X.S.Z. and H.W. acknowledge the financial support from the U.S. Defense Advanced Research Projects Agency (DARPA) Young Faculty Award (N660012314013). This material is based upon Q.C.'s work supported by the Air Force Office of Scientific Research under award number FA9550-23-1-0609. E.R.N. acknowledges support from NIH R01 CA234025. R.B. acknowledges the support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number T32EB019944. J.H. acknowledges the support from the Cancer Scholars for Translational and Applied Research (C*STAR) Program sponsored by the Cancer Center at Illinois and the Carle Cancer Center under Award Number CST EP012023.
PY - 2023/12
Y1 - 2023/12
N2 - 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 survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines.
AB - 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 survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines.
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UR - http://www.scopus.com/inward/citedby.url?scp=85178850704&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-43914-8
DO - 10.1038/s41467-023-43914-8
M3 - Article
C2 - 38052869
AN - SCOPUS:85178850704
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 8047
ER -