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
Xia (2020) Folate functionalized pH-sensitive photothermal therapy traceable hollow mesoporous silica nanoparticles as a targeted drug carrier to improve the antitumor effect of doxorubicin in the hepatoma cell line SMMC-
Spinal cord injury (SCI) is an extremely destructive central nervous system lesion. Studies have shown that NGF can promote nerve regeneration after SCI. However, it cannot produce the desired effect due to its stability in the body and is difficulty in passing through the blood-brain barrier. In this study, we prepared nanovesicles derived from macrophage membrane encapsulating NGF (NGF-NVs) as a drug carrier for the treatment of SCI. Cell experiments showed that NGF-NVs were effectively taken up by PC12 cells and inhibited neuronal apoptosis. In vivo imaging experiments, a large quantity of NGF was delivered to the injured site with the aid of the good targeting of NVs. In animal experiments, NGF-NVs improved the survival of neurons by significantly activating the PI3K/AKT signaling pathway and had good behavioral and histological recovery effects after SCI. Therefore, NVs are a potential drug delivery vector for SCI therapy.
This study aims to investigate the potential therapeutic effect of exosomes derived from macrophages loaded with curcumin (Exos-cur) on the healing of diabetic wounds. As a new type of biomaterial, Exos-cur has better stability, antiinflammation, and antioxidation biological activity. In in vitro experiments, Exos-cur can promote the proliferation, migration, and angiogenesis of HUVECs (human umbilical vein endothelial cells) while reducing the ROS (reactive oxygen species) produced by HUVECs induced by high glucose, regulating the mitochondrial membrane potential, reducing cell oxidative damage, and inhibiting oxidative stress and inflammation. In the in vivo experiment, the Exos-cur treatment group had an increased percentage of wound closure and contraction compared with the diabetic wound control group. Hematoxylin−eosin staining (HE) and Masson staining showed that the Exos-cur treatment group had more advanced reepithelialization, and the generated mature granulation tissue was rich in a large number of capillaries and newly deposited collagen fibers. Western blot and immunofluorescence analyses showed that Exos-cur can inhibit inflammation by activating the Nrf2/ARE pathway, upregulate the expression of wound healing-related molecules, promote angiogenesis, and accelerate wound healing in diabetic rats. These results show that Exos-cur has a good therapeutic effect on diabetic skin defects and provide experimental evidence for the potential clinical benefits of Exos-cur.
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