Bioactivity and cellular uptake of distinct nanoparticles in human endothelial cells

纳米粒子在环境中无处不在，随着工业的大量生产，其数量也在不断增加。这会导致人体持续暴露于NP。由于我们不能通过呼吸道系统、胃肠道和皮肤逃脱NP的摄取，穿过这些生理屏障的NPs将进入被内皮细胞(EC)覆盖的血液和淋巴管系统。这些细胞在控制炎症、凝血、血流和血压方面起着至关重要的作用。因此，EC活性的任何紊乱都可能导致炎症或凝血状态，对人类健康产生重大影响。我们团队的跨学科方法使我们能够分析NPs(由Reller教授(资源战略)设计)对人类EC(Hilger教授(医学))的生物活性，使用单个NP示踪显微镜(Bruäuchle教授(生物物理化学)、声驱动微流体和脂膜作为细胞膜的简单模型(Wixforth教授(纳米技术))的组合强度)。通过在芯片上的微流控实验室中直接生长内皮细胞，模拟我们人工血管的生理条件，我们将在短时间尺度和长时间尺度(几分钟到几天)上研究纳米粒子对人血管内皮细胞的生物活性和毒性。我们的微流体系统具有光学可及性和体积小的特点，使我们能够通过荧光检测生物活性，通过细胞内的凋亡标志物、细胞内信号以及促炎和凝血蛋白的释放来检测内皮细胞的炎症反应和毒性。此外，利用NP跟踪显微镜和控制NP细胞碰撞速率和局部NP浓度的微流控反应器组成的混合技术，可以详细地监测摄取速率和途径。监测NPs与脂膜的相互作用是从物理角度了解NPs对细胞膜的影响的有价值的工具。所有获得的结果都将与NP类型和大小相关。

Nanoparticles (NPs) are omnipresent in the environment and their quantity increases constantly as they are produced in large numbers by the industry. This leads to a constant NP exposure of the human body. As we are not able to escape NP uptake via the airway system, gastro-intestinal tract and skin, NPs crossing these physiological barriers will enter the blood and lymphatic vessel system which is covered by endothelial cells (EC). These cells play an essential role concerning the control of inflammation, coagulation, blood flow and blood pressure. Therefore, any disturbance of EC activity may lead to inflammatory or coagulatory conditions with great impact on human health. The interdisciplinary approach of our team allows us to analyze the bioactivity of NPs (designed by Prof. Reller (Resource Strategy)) on human EC (Prof. Hilger (medicine)) using the combined strength of single NP tracing microscopy (Prof. Bräuchle (biophysical chemistry)), acoustically driven microfluidics and lipid membranes as simple models for cell membranes (Prof. Wixforth (nanotechnology)). Mimicking the physiological conditions of our artificial blood vessels by growing EC directly on a microfluidic lab on a chip, we will study the bioactivity and toxicity of NPs on human EC on short and long time scales (minutes to days). The optical accessibility and small size of our microfluidic system enables us to detect bioactivity by means of fluorescence, inflammatory response and toxicity of ECs by apoptotic markers, intracellular signalling and proinflammatory and coagulatory protein release. In addition uptake rates and pathways can be monitored in detail by applying the hybrid technique composed of NP tracking microscopy and the microfluidic reactor which controls NP-cell collision rate and local NP concentration. Monitoring the interactions of NPs with lipid membranes is a valuable tool to understand the impact of NPs on the cell membrane from a physical point of view. All gained results will be correlated to NP type and size.