4.7 Article

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

Journal

JOURNAL OF EXTRACELLULAR VESICLES
Volume 10, Issue 5, Pages -

Publisher

WILEY
DOI: 10.1002/jev2.12077

Keywords

biodistribution; bioorthogonal copper-free dick chemistry; CD44-targeting; extracellular vesicles; metabolic glycoengineering

Categories

Funding

  1. Basic Science Research Program of the National Research Foundation (NRF) [2018R1A2B3006080]
  2. Korea Basic Science Institute (National Research Facilities and Equipment Center) grant of the Ministry of Education [2020R1A6C101A191]
  3. Korea Heath Technology R&D Project of the Ministry of Health & Welfare, Republic of Korea [HI20C0437]
  4. National Research Foundation of Korea [4120200813689, 4199990313935] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This study successfully prepared surface-edited EVs using bioorthogonal copper-free click chemistry and metabolic glycoengineering, which effectively accumulated in target tissues in animal models, primarily due to prolonged circulation in the bloodstream and active targeting mechanism.
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.

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