Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy
Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy
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表面功能化外泌体作为脑缺血治疗的靶向药物递送载体
DOI：
10.1016/j.biomaterials.2017.10.012
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发表时间：
2018-01-01
期刊：
影响因子：
14
通讯作者：
Gao, Jun
中科院分区：
文献类型：
--
作者：
Tian, Tian;Zhang, Hui-Xin;Gao, Jun
安全有效的药物输送是缺血性卒中治疗的主要障碍。外泌体作为治疗脑缺血的内源性药物递送纳米系统具有很大的前景，因为它们具有独特的性质，包括低免疫原性、先天稳定性、高递送效率和穿过血脑屏障（BBB）的能力。然而，外泌体靶向能力不足限制了其临床应用。在这项研究中，c（RGDyK）肽已经通过简单，快速和生物正交化学缀合到外泌体表面。在短暂性大脑中动脉闭塞（MCAO）小鼠模型中，经静脉给药后，工程化c（RGDyK）缀合的exosomes（cRGD-Exo）靶向缺血脑的病变区域。此外，姜黄素已被加载到cRGD-Exo上，并且这些外泌体的施用导致了对病变区域中的炎症反应和细胞凋亡的强烈抑制。这些结果提示了基于exosomes的缺血脑靶向递送载体，并为功能化exosomes的快速和大规模生产提供了策略。(C)2017爱思唯尔有限公司版权所有
The safe and effective delivery of drugs is a major obstacle in the treatment of ischemic stroke. Exosomes hold great promise as an endogenous drug delivery nanosystem for the treatment of cerebral ischemia given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and ability to cross the blood-brain barrier (BBB). However, exosome insufficient targeting capability limits their clinical applications. In this study, the c(RGDyK) peptide has been conjugated to the exosome surface by an easy, rapid, and bio-orthogonal chemistry. In the transient middle cerebral artery occlusion (MCAO) mice model, The engineered c(RGDyK)-conjugated exosomes (cRGD-Exo) target the lesion region of the ischemic brain after intravenous administration. Furthermore, curcumin has been loaded onto the cRGD-Exo, and administration of these exosomes has resulted in a strong suppression of the inflammatory response and cellular apoptosis in the lesion region. The results suggest a targeting delivery vehicle for ischemic brain based on exosomes and provide a strategy for the rapid and large-scale production of functionalized exosomes. (C) 2017 Elsevier Ltd. All rights reserved.