Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury.
Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury.
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DOI：
10.1016/j.bioactmat.2022.11.011
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发表时间：
2023-05
影响因子：
18.9
通讯作者：
Cai, Weihua
中科院分区：
文献类型：
--
作者：
Rong, Yuluo;Wang, Zhuanghui;Tang, Pengyu;Wang, Jiaxing;Ji, Chengyue;Chang, Jie;Zhu, Yufeng;Ye, Wu;Bai, Jianling;Liu, Wei;Yin, Guoyong;Yu, Lipeng;Zhou, Xuhui;Cai, Weihua
关键词：
脊髓损伤（SCI）是一种严重的神经系统疾病，会导致不可修复的损伤和功能丧失，迄今为止还没有有效的治疗方法。携带治疗分子的工程化细胞外囊泡（EV）有望作为替代SCI治疗，这取决于特定的功能化EV和适当的工程化策略。在这项研究中，我们展示了用于SCI靶向治疗的肽CAQK修饰的siRNA负载的EV（C-EVs-siRNA）的药物递送系统的设计。通过化学修饰将肽CAQK锚定到从诱导的神经干细胞（iNSC）分离的EV的膜。然后通过电穿孔将CCL 2-siRNA加载到EV中。修饰后的EV仍保持EV的基本特性，并在体内外显示出良好的靶向性和治疗效果。C-EVs-siRNA特异性地将siRNA递送到SCI区域并被靶细胞摄取。C-EVs-siRNA利用iNSC衍生的EV的固有抗炎和神经修复功能与负载的siRNA协同作用，从而增强针对SCI的治疗效果。靶向修饰的EV和siRNA的组合有效地调节了SCI后的微环境紊乱，促进了小胶质细胞/巨噬细胞从M1向M2的转化，并限制了炎症反应和神经元损伤对SCI后小鼠功能恢复的负面影响。因此，工程EV是SCI的潜在可行和有效的治疗方法，也可用于开发其他疾病的靶向治疗。携带治疗分子的工程电动汽车有望成为替代SCI疗法。C-EVs-siRNA可以特异性地将siRNA递送到SCI区域并被靶细胞摄取。C-EVs-siRNA利用EV固有的神经修复功能，并与加载的siRNA协同作用。C-EVs-siRNA可调节脊髓损伤后微环境紊乱，促进运动功能恢复。C-EVs-siRNA是一种潜在可行且有效的SCI治疗方法。
Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo. C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells. C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA, thus enhancing the therapeutic effect against SCI. The combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI, promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after SCI. Thus, engineered EVs are a potentially feasible and efficacious treatment for SCI, and may also be used to develop targeted treatments for other diseases. Engineered EVs carrying therapeutic molecules hold promise as an alternative SCI therapy. C-EVs-siRNA can specifically deliver siRNA to SCI areas and be taken up by target cells. C-EVs-siRNA used the inherent neuroreparative functions of EVs and acted synergistically with the loaded siRNA. C-EVs-siRNA modulated microenvironmental disturbance and promoted motor function recovery after SCI. C-EVs-siRNA were a potentially viable and efficacious treatment for SCI.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
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影响因子：
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Lokanathan Y
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11.4
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通讯作者：
Cai W
影响因子：
2.4
作者：
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通讯作者：
Ghogawala, Zoher