Institute of Anesthesiology, University Hospital Zurich, Hof E 111, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Institute of Physiology & Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Nanomedicine (Lond). 2015;10(24):3537-46. doi: 10.2217/nnm.15.172. Epub 2015 Oct 5.
Magnetic field guided drug targeting holds promise for more effective cancer treatment. Intravascular application of magnetic nanoparticles, however, bears the risk of potentially important, yet poorly understood side effects, such as off-target accumulation in endothelial cells.
MATERIALS & METHODS: Here, we investigated the influence of shear stress (0-3.22 dyn/cm(2)), exposure time (5-30 min) and endothelial activation on the uptake of ferromagnetic carbon-encapsulated iron carbide nanomagnets into endothelial cells in an in vitro flow cell model.
We found that even moderate shear stresses typically encountered in the venous system strongly reduce particle uptake compared with static conditions. Interestingly, a pronounced particle uptake was observed in inflamed endothelial cells.
This study highlights the importance of relevant exposure scenarios accounting for physiological conditions when studying particle-cell interactions as, for example, shear stress and endothelial activation are major determinants of particle uptake. Such considerations are of particular importance with regard to successful translation of in vitro findings into (pre-)clinical end points.
磁场引导药物靶向具有提高癌症治疗效果的潜力。然而，血管内应用磁性纳米粒子存在潜在重要但了解甚少的副作用风险，例如在血管内皮细胞中的非靶部位聚集。
本研究在体外流动细胞模型中，研究了切应力（0-3.22 dyn/cm(2)）、暴露时间（5-30 分钟）和内皮细胞激活对铁碳纳米磁珠进入内皮细胞摄取的影响。
我们发现，即使是静脉系统中常见的中等切应力也会强烈降低与静态条件相比的颗粒摄取。有趣的是，在炎症性内皮细胞中观察到明显的颗粒摄取。
本研究强调了在研究颗粒-细胞相互作用时，考虑相关暴露情况的重要性，包括生理条件，因为切应力和内皮细胞激活是颗粒摄取的主要决定因素。在将体外研究结果转化为（临床前）临床终点时，这些考虑尤为重要。
