Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases

Gyeong Taek Lim, Dong Gil You, Hwa Seung Han, Hansang Lee, Sol Shin, Byeong Hoon Oh, E. K.Pramod Kumar, Wooram Um, Chan Ho Kim, Seungsu Han, Sangho Lee, Seungho Lim, Hong Yeol Yoon, Kwangmeyung Kim, Ick Chan Kwon, Dong Gyu Jo, Yong Woo Cho, Jae Hyung Park

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 azide 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.

Original languageEnglish
Article numbere12077
JournalJournal of Extracellular Vesicles
Volume10
Issue number5
DOIs
Publication statusPublished - 2021 Mar
Externally publishedYes

Keywords

  • CD44-targeting
  • biodistribution
  • bioorthogonal copper-free click chemistry
  • extracellular vesicles
  • metabolic glycoengineering

ASJC Scopus subject areas

  • Histology
  • Cell Biology

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