Journal of Nanobiotechnology | |
Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury | |
He Tian1  Chuanjie Zhang2  Daoyong Li2  Hengshuo Hu2  Xifan Mei2  Kaihua Zhang2  Zhe Wang2  Jinyu An3  Chao Wu3  Zhanshan Gao3  | |
[1] Department of Histology and Embryology, Jinzhou Medical University;Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University;Pharmacy School, Jinzhou Medical University; | |
关键词: Spinal cord injury; Extracellular vesicles; Curcumin; M2 repolarization; Neuroprotection; | |
DOI : 10.1186/s12951-021-01123-9 | |
来源: DOAJ |
【 摘 要 】
Abstract Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. Results By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. Conclusions A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI. Graphical Abstract
【 授权许可】
Unknown