Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain.
Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain.
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DOI：
10.1016/j.biomaterials.2017.07.011
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发表时间：
2017-10
期刊：
影响因子：
14
通讯作者：
Kabanov AV
中科院分区：
文献类型：
--
作者：
Yuan D;Zhao Y;Banks WA;Bullock KM;Haney M;Batrakova E;Kabanov AV
最近的工作激发了人们对使用外泌体作为纳米载体将小分子药物、RNA和蛋白质递送至中枢神经系统（CNS）的兴趣。为了克服血脑屏障（BBB），用靶向脑内皮但可能增加免疫应答的脑归巢肽修饰外泌体。在这里，我们第一次证明，在哺乳动物中，没有必要进行这样的修饰来穿透血脑屏障。幼稚巨噬细胞（幼稚巨噬细胞）外泌体可以利用，1）一方面，整联蛋白淋巴细胞功能相关抗原1（LFA-1）和细胞间粘附分子1（ICAM-1），和2）另一方面，碳水化合物结合C型凝集素受体，与包含BBB的脑微血管内皮细胞相互作用。值得注意的是，ICAM-1的上调（炎症中的常见过程）促进BBB细胞中的M β外泌体摄取。我们在体内进一步证明，静脉内（IV）给药后，幼稚的M β外泌体穿过BBB并将货物蛋白（脑源性神经营养因子（BDNF））递送至大脑。这种递送在脑炎症的存在下得到增强，脑炎症是CNS疾病中经常存在的一种病症。总的来说，这些发现对基础科学和可能使用来自M β的外泌体作为纳米载体用于脑递送治疗性蛋白质以治疗CNS疾病感兴趣。
Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB. Notably, upregulation of ICAM-1, a common process in inflammation, promotes Mϕ exosomes uptake in the BBB cells. We further demonstrate in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the BBB and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain. This delivery is enhanced in the presence of brain inflammation, a condition often present in CNS diseases. Taken together, the findings are of interest to basic science and possible use of Mϕ-derived exosomes as nanocarriers for brain delivery of therapeutic proteins to treat CNS diseases.
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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.
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
9.3
作者：
Dickens, Alex M.;Vainio, Susanne;Airas, Laura
通讯作者：
Airas, Laura
影响因子：
4.4
作者：
Chen, Ching-Long;Liang, Chang-Min;Chen, Jiann-Torng
通讯作者：
Chen, Jiann-Torng
外泌体的细胞内化通过吞噬作用发生
影响因子：
4.5
作者：
Feng, Du;Zhao, Wen-Long;Sui, Sen-Fang
通讯作者：
Sui, Sen-Fang