Macromol Biosci:外泌体修饰的组织工程血管可实现内皮祖细胞的捕获和siRNA的靶向递送

2017-12-09 MedSci MedSci原创

不稳定和较差的靶向性是导致RNA修饰的组织工程血管(TEBV)长期效果较差的主要原因。 可以在外泌体中富集RNA,然后将其递送到靶细胞中,而外泌体修饰的TEBV是否实现RNA的靶向递送目前尚不清楚。本研究中,为了促进间质干细胞(MSC)来源的外泌体上klotho蛋白的表达,首先将klotho质粒转染到MSsC中,然后使用电穿孔方法将腺苷激酶(ADK)siRNA加载到外泌体(klotho/ADK s

不稳定和较差的靶向性是导致RNA修饰的组织工程血管(TEBV)长期效果较差的主要原因。 可以在外泌体中富集RNA,然后将其递送到靶细胞中,而外泌体修饰的TEBV是否实现RNA的靶向递送目前尚不清楚。

本研究中,为了促进间质干细胞(MSC)来源的外泌体上klotho蛋白的表达,首先将klotho质粒转染到MSsC中,然后使用电穿孔方法将腺苷激酶(ADK)siRNA加载到外泌体(klotho/ADK siRNA-外泌体)。流室结果显示,klotho/ADK siRNA-exosome能够有效捕获循环内皮祖细胞(EPCs)。此外,捕获的EPCs可以胞吞这个外泌体,然后分解成klotho蛋白和ADK siRNA。ADK siRNA还能促进EPCs的促血管生成因子和腺苷的旁分泌,进一步促进内皮细胞的增殖和迁移。基于聚乙烯亚胺封端的金纳米颗粒,通过逐层组装构建外泌体修饰的TEBV。动物实验结果显示,klotho/ADK siRNA-外泌体修饰的TEBVs可以保持一个月的血液通畅性,并观察到良好的内皮化作用。

总之,该研究结果显示,本研究成功构建了exosome修饰的TEBV,可捕获外泌体表面的分子,并捕获循环EPCs,负载的RNA可根据患者的治疗需要达到了精确治疗的目的。

原始出处:


Chen W, Yang M, et al., Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery. Macromol Biosci. 2017 Dec 4. doi: 10.1002/mabi.201700242.

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    2018-11-19 yb6560
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    2018-06-30 sunylz
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    2017-12-11 10518094zz
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    2017-12-11 zhangyxzsh

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