Investigation of biomimetic shear stress on cellular uptake and mechanism of polystyrene nanoparticles in various cancer cell lines
Investigation of biomimetic shear stress on cellular uptake and mechanism of polystyrene nanoparticles in various cancer cell lines
复制标题
DOI：
10.1007/s12272-016-0847-0
复制
发表时间：
2016-12-01
影响因子：
6.7
通讯作者：
Lee, Beom-Jin
中科院分区：
文献类型：
--
作者：
Kang, Taehee;Park, Chulhun;Lee, Beom-Jin
肿瘤微环境中的癌细胞受到由血管微环境中的血流和肿瘤微环境中的间质流产生的流体剪切应力的影响。因此，我们研究了流体剪切应力如何影响细胞摄取以及纳米颗粒的内吞机制，使用仿生微流体系统，模仿人类的动态环境。在静态和仿生动态条件下（0.5达因/厘米（2）），将100微克/毫升的带正电荷的氨基改性聚苯乙烯纳米粒子（PSN）输送到癌细胞。此外，实验是在对内吞途径之一具有特异性的内吞抑制剂的存在下进行的。为了评估阳离子PSN的细胞摄取，通过流式细胞仪测量癌细胞中阳离子PSN的荧光强度，并使用共聚焦激光扫描显微镜拍摄荧光图像。动态条件下的癌细胞表现出较高的细胞摄取PSN，并显示出不同的细胞摄取机制相比，在静态条件下。从这些结果可以看出，仿生动力学条件刺激了特异性内吞作用，促进了细胞摄取。考虑流体剪切应力作为关键因素之一也是重要的，因为细胞摄取和药物递送在癌细胞和转移中起关键作用。
Cancer cells in the tumor microenvironment are affected by fluid shear stress generated by blood flow in the vascular microenvironment and interstitial flows in the tumor microenvironment. Thus, we investigated how fluidic shear stress affects cellular uptake as well as the endocytosis mechanism of nanoparticles using a biomimetic microfluidic system that mimics the human dynamic environment. Positively charged amino-modified polystyrene nanoparticles (PSNs) at 100 mu g/mL were delivered to cancer cells under static and biomimetic dynamic conditions (0.5 dyne/cm(2)). Additionally, the experiment was done in the presence of endocytosis inhibitors specific for one of the endocytosis pathways. To evaluate cellular uptake of cationic PSNs, the fluorescence intensity of cationic PSNs in cancer cells was measured by flow cytometer and fluorescence images were taken using confocal laser scanning microscopy. Cancer cells in dynamic conditions exhibited higher cellular uptake of PSNs and showed different cellular uptake mechanisms compared with those in static conditions. From these results, it suggested that biomimetic dynamic conditions stimulated specific endocytosis and prompted cellular uptake. It was also important to consider fluidic shear stress as one of the critical factors because cellular uptake and drug delivery could play a key role in cancer cells and metastasis.