Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries

Acta Pharmaceutica Sinica B, 2023 · DOI: https://doi.org/10.1016/j.apsb.2022.06.007 · Published: May 1, 2023

Simple Explanation

The study focuses on treating central nervous system (CNS) injuries like stroke by using extracellular vesicles (EVs) from M2 microglia. These EVs are modified with a peptide (DA7R) that targets injured blood vessels and a chemokine (SDF-1) that attracts stem cells. This modification, done via click chemistry, aims to create a nanocarrier (Dual-EV) that can specifically deliver regenerative signals to the injured site, promoting the differentiation of neural stem cells (NSCs) into neurons. In stroke model mice, Dual-EV nanocarriers were shown to accumulate in the ischemic area, recruit NSCs, and increase neurogenesis, suggesting a potential new approach for treating neuronal damage after CNS injuries.

Study Duration

Not specified

Participants

ICR mice (30e35 g)

Evidence Level

Not specified

Key Findings

1
Dual-EV nanocarriers target human umbilical vascular endothelial cells (HUVECs) and recruit NSCs in vitro.
2
Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice.
3
Dual-EV treatment enhances neurogenesis in vivo, as evidenced by increased Nestin-positive cells in the SVZ and DCX-positive cells in the SVZ and striatum regions.

Research Summary

This study introduces a novel approach for treating CNS injuries, particularly stroke, by utilizing engineered extracellular vesicles (EVs) derived from M2 microglia. The EVs are modified with DA7R and SDF-1 via copper-free click chemistry to enhance their targeting ability to injured blood vessels and recruit neural stem cells (NSCs). In vivo experiments demonstrate that these dual-modified EVs (Dual-EV) accumulate in the ischemic area of stroke model mice, promote NSC recruitment, increase neurogenesis, and improve neurological function recovery.

Practical Implications

Therapeutic Development

The Dual-EV nanocarriers show promise as a novel therapeutic approach for promoting neuronal regeneration and functional recovery after CNS injuries, particularly stroke.

Drug Delivery

The click chemistry-based modification of EVs provides a versatile platform for targeted drug delivery to specific locations within the CNS.

Stem Cell Therapy

The findings support the development of strategies that enhance endogenous stem cell recruitment and differentiation for tissue repair in the CNS.

Study Limitations

1
The precise mechanisms by which M2-EVs induce NSCs to differentiate into neurons require further investigation.
2
Increasing the yield and reducing the loss of engineered EVs during the modification process remains a challenge.
3
The rapid clearance of EVs during blood circulation may limit their therapeutic capabilities, necessitating strategies to modulate their pharmacokinetic properties.

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