Nitric Oxide Release in Human Aortic Endothelial Cells Mediated by Delivery of Amphiphilic Polysiloxane Nanoparticles to Caveolae
Nitric Oxide Release in Human Aortic Endothelial Cells Mediated by Delivery of Amphiphilic Polysiloxane Nanoparticles to Caveolae
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DOI：
10.1021/bm900128x
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发表时间：
2009-08-01
影响因子：
6.2
通讯作者：
Kadokawa, Jun-ichi
中科院分区：
文献类型：
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作者：
Nishikawa, Takehiro;Iwakiri, Norio;Kadokawa, Jun-ichi
脂筏和细胞膜穴等微结构域被组织为细胞质膜中的功能区室。在本研究中，我们注意到小凹的功能平台具有双重功能，即外部物质的内化和导致一氧化氮释放的细胞信号传导，并假设内皮一氧化氮合酶的酶活性的转换可以通过纳米颗粒靶向小凹来实现。我们制备了聚硅氧烷纳米颗粒，并研究了纳米颗粒的细胞摄取及其对人主动脉内皮细胞中一氧化氮释放的影响。我们发现聚硅氧烷纳米颗粒通过人主动脉内皮细胞中的小窝被内吞，并且纳米颗粒的细胞摄取增强了一氧化氮的释放。此外，我们证实内皮一氧化氮合酶在细胞摄取纳米粒子的过程中被激活。这些发现支持我们的观点，即将聚合物纳米颗粒递送至内皮细胞可以诱导一氧化氮的释放。
Microdomains such as lipid raft and caveolae are organized as functional compartments in plasma membrane of cells. In this study, we note the functional platform of caveolae with dual functions, internalization of external substances and cell signalings leading to nitric oxide release, and hypothesize that the switching of enzyme activity of endothelial nitric oxide synthase can be achieved by targeting caveolae with nanoparticles. We prepared polysiloxane nanoparticles and studied cellular uptake of the nanoparticles and its concomitant influence on the nitric oxide release in human aortic endothelial cells. We found that polysiloxane nanoparticles were endocytosed via caveolae in human aortic endothelial cells and that enhanced nitric oxide release was followed by the cellular uptake of the nanoparticles. Furthermore, we confirmed that endothelial nitric oxide synthase was activated during cellular uptake of the nanoparticles. These findings support our idea that delivery of the polymeric nanoparticles to endothelial cells can lead to the induction of nitric oxide release.