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Feasibility of Mechanical Extrusion to Coat Nanoparticles with Extracellular Vesicle Membranes.
Cells ( IF 5.1 ) Pub Date : 2020-07-29 , DOI: 10.3390/cells9081797
Jan Van Deun 1, 2 , Quentin Roux 1, 2 , Sarah Deville 1, 2 , Thibaut Van Acker 3 , Pekka Rappu 4 , Ilkka Miinalainen 5 , Jyrki Heino 4 , Frank Vanhaecke 3 , Bruno G De Geest 6 , Olivier De Wever 1, 2 , An Hendrix 1, 2
Affiliation  

Biomimetic functionalization to confer stealth and targeting properties to nanoparticles is a field of intense study. Extracellular vesicles (EV), sub-micron delivery vehicles for intercellular communication, have unique characteristics for drug delivery. We investigated the top-down functionalization of gold nanoparticles with extracellular vesicle membranes, including both lipids and associated membrane proteins, through mechanical extrusion. EV surface-exposed membrane proteins were confirmed to help avoid unwanted elimination by macrophages, while improving autologous uptake. EV membrane morphology, protein composition and orientation were found to be unaffected by mechanical extrusion. We implemented complementary EV characterization methods, including transmission- and immune-electron microscopy, and nanoparticle tracking analysis, to verify membrane coating, size and zeta potential of the EV membrane-cloaked nanoparticles. While successful EV membrane coating of the gold nanoparticles resulted in lower macrophage uptake, low yield was found to be a significant downside of the extrusion approach. Our data incentivize more research to leverage EV membrane biomimicking as a unique drug delivery approach in the near future.

中文翻译:

机械挤压用细胞外囊泡膜包裹纳米颗粒的可行性。

仿生功能化为纳米粒子赋予隐形和靶向特性是一个深入研究的领域。细胞外囊泡(EV)是用于细胞间通讯的亚微米传递载体,具有独特的药物传递特征。我们通过机械挤压研究了具有细胞外囊泡膜的金纳米粒子的自上而下的功能化,包括脂质和相关的膜蛋白。证实EV表面暴露的膜蛋白可帮助避免巨噬细胞不必要的清除,同时改善自体摄取。发现EV膜的形态,蛋白质组成和方向不受机械挤压的影响。我们实施了互补的EV表征方法,包括透射电子显微镜和免疫电子显微镜以及纳米颗粒跟踪分析,验证EV膜隐蔽纳米颗粒的膜涂层,尺寸和Zeta电位。尽管成功的金纳米颗粒的EV膜涂层导致巨噬细胞摄取降低,但发现低产量是挤出方法的重要缺点。我们的数据激励着更多的研究在不久的将来将EV膜仿生技术用作独特的药物递送方法。
更新日期:2020-07-29
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