Department of Biotechnology , University of Natural Resources and Life Sciences , Vienna , Austria.
Department of Medicine III , Medical University Vienna , Vienna , Austria.
Anal Chem. 2018 Mar 20;90(6):3651-3655. doi: 10.1021/acs.analchem.7b04788. Epub 2018 Feb 28.
In the present work, we combine experimental and computational methods to define the critical shear stress as an alternative parameter for nanotoxicological and nanomedical evaluations using an in vitro microfluidic vascular model. We demonstrate that our complementary in vitro and in silico approach is well suited to assess the fluid flow velocity above which clathrin-mediated (active) nanoparticle uptake per cell decreases drastically although higher numbers of nanoparticles per cell are introduced. Results of our study revealed a critical shear stress of 1.8 dyn/cm, where maximum active cellular nanoparticle uptake took place, followed by a 70% decrease in uptake of 249 nm nanoparticles at 10 dyn/cm, respectively. The observed nonlinear relationship between flow velocity and nanoparticle uptake strongly suggests that fluid mechanical forces also need to be considered in order to predict potential in vivo distribution, bioaccumulation, and clearance of nanomaterials and novel nanodrugs.
在本工作中，我们结合实验和计算方法，通过体外微流控血管模型，定义了临界剪切应力作为纳米毒理学和纳米医学评估的替代参数。我们证明，我们的体外和计算方法具有很好的互补性，适用于评估细胞摄取网格蛋白介导（主动）纳米颗粒的流速，尽管每个细胞引入的纳米颗粒数量更多，但流速超过临界值后，细胞摄取的纳米颗粒数量会急剧减少。我们的研究结果揭示了临界剪切应力为 1.8 dyn/cm，在此剪切应力下，细胞主动摄取纳米颗粒的数量达到最大值，而在 10 dyn/cm 时，细胞摄取 249nm 纳米颗粒的数量则减少了 70%。观察到的流速与纳米颗粒摄取之间的非线性关系强烈表明，为了预测纳米材料和新型纳米药物的潜在体内分布、生物累积和清除，还需要考虑流体力学力。
