Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication.
Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication.
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DOI：
10.1007/s12195-016-0457-4
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发表时间：
2016-09
影响因子：
2.8
通讯作者：
Jay, Steven M.
中科院分区：
文献类型：
--
作者：
Lamichhane, Tek N.;Jeyaram, Anjana;Patel, Divya B.;Parajuli, Babita;Livingston, Natalie K.;Arumugasaamy, Navein;Schardt, John S.;Jay, Steven M.
关键词：
细胞外囊泡（EV），包括外来体和微囊泡，由于其在细胞间RNA转运中的天然作用，已经成为小RNA（siRNA和miRNA）的有希望的药物递送载体。然而，EV用于治疗性RNA递送的应用可能受到可诱导货物聚集或降解的加载方法的限制。在这里，我们报告了使用超声处理作为一种手段，积极加载功能性小RNA到EV。鉴定了EV可以负载具有最小可检测聚集的小RNA的条件，并且观察到通过超声处理负载有治疗性siRNA的EV被受体细胞摄取并且能够靶mRNA敲低，导致蛋白质表达降低。该系统最终被应用于降低HER2的表达，HER2是一种致癌受体酪氨酸激酶，其关键介导乳腺癌的发展和进展，并且可以扩展到其他治疗靶点。这些结果定义了通知超声处理作为EV的小RNA加载方法的应用的重要参数，并证明了这种方法用于多功能癌症治疗的潜在实用性。
Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising drug delivery vehicles for small RNAs (siRNA and miRNA) due to their natural role in intercellular RNA transport. However, the application of EVs for therapeutic RNA delivery may be limited by loading approaches that can induce cargo aggregation or degradation. Here, we report the use of sonication as a means to actively load functional small RNAs into EVs. Conditions under which EVs could be loaded with small RNAs with minimal detectable aggregation were identified, and EVs loaded with therapeutic siRNA via sonication were observed to be taken up by recipient cells and capable of target mRNA knockdown leading to reduced protein expression. This system was ultimately applied to reduce expression of HER2, an oncogenic receptor tyrosine kinase that critically mediates breast cancer development and progression, and could be extended to other therapeutic targets. These results define important parameters informing the application of sonication as a small RNA loading method for EVs and demonstrate the potential utility of this approach for versatile cancer therapy.
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DOI：
10.1016/j.jconrel.2014.12.013
发表时间：
2015-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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