Lim, Gyeong Taek You, Dong Gil Han, Hwa Seung Lee, Hansang Shin, Sol Oh, Byeong Hoon Kumar, E. K. Pramod Um, Wooram Kim, Chan Ho Han, Seungsu Lee, Sangho Lim, Seungho Yoon, Hong Yeol Kim, Kwangmeyung Kwon, Ick Chan Jo, Dong-Gyu Cho, Yong Woo Park, Jae Hyung 2024-01-19T15:05:22Z 2024-01-19T15:05:22Z 2021-09-05 2021-03 2001-3078 https://pubs.kist.re.kr/handle/201004/117325 Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action. Herein, based on bioorthogonal copper-free click chemistry (BCC), surface-edited EVs were prepared by using metabolically glycoengineered cells. First, the exogenous aside group was generated on the cellular surface through metabolic glycoengineering (MGE) using the precursor. Next, PEGylated hyaluronic acid, capable of binding specifically to the CD44 -expressing cells, was labelled as the representative targeting moiety onto the cell surface by BCC. The surface-edited EVs effectively accumulated into the target tissues of the animal models with rheumatoid arthritis and tumour, primarily owing to prolonged circulation in the bloodstream and the active targeting mechanism. Overall, these results suggest that BCC combined with MGE is highly useful as a simple and safe approach for the surface modification of EVs to modulate their in vivo fate. English Co-Action Publishing Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases Article 10.1002/jev2.12077 1 Journal of Extracellular Vesicles, v.10, no.5 Journal of Extracellular Vesicles 10 5 Y scie scopus 000632839300003 2-s2.0-85102878010 Cell Biology Cell Biology Article biodistribution bioorthogonal copper-free dick chemistry CD44-targeting extracellular vesicles metabolic glycoengineering