Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries
Name
1-s2.0-S2211383522002751-nc nd.pdf
Description
Published version
Size
5.1 MB
Format
Adobe PDF
Checksum (MD5)
64d175a38392f543af73427877667501
Author(s)
Ruan, Huitong
Li, Yongfang
Wang, Cheng
Jiang, Yixu
Han, Yulong
Li, Yiwei
Zheng, Dandan
Ye, Jing
Chen, Gang
Yang, Guo-yuan
Date Issued
May 2023
Journal
Acta Pharmaceutica Sinica B
Publisher
Elsevier BV
Citation
Ruan, Huitong, Li, Yongfang, Wang, Cheng, Jiang, Yixu, Han, Yulong et al. 2023. "Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries." Acta Pharmaceutica Sinica B, 13 (5).
Version
Final published version
Abstract
Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.
MIT Department
Massachusetts Institute of Technology. School of Engineering
Terms of Use
Creative Commons Attribution Noncommercial No Derivatives
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DOI of Published Version
10.1016/j.apsb.2022.06.007
