论文标题
肺表面活性剂抑制肺泡上皮细胞的纳米颗粒摄取
Pulmonary surfactant inhibition of nanoparticle uptake by alveolar epithelial cells
论文作者
论文摘要
肺部表面活性剂形成覆盖肺泡腔表面和吸入的纳米颗粒表面的亚微米厚的流体层，因此在与上皮细胞的任何相互作用之前就与表面活性剂接触。我们通过在体外使用二氧化硅 - 曲面上皮细胞系统对相互作用进行建模，研究表面活性剂作为保护性物理屏障的作用。电子显微镜显示，囊泡在存在纳米颗粒的情况下保存，而纳米粒子脂质相互作用会导致形成混合聚集体。荧光显微镜显示，表面活性剂可在两种模型的肺泡上皮细胞A549和NCI-H441中降低纳米颗粒的摄取多达两个数量级，而与Transwell上的玻璃或空气界面培养上无关。共聚焦显微镜通过显示纳米颗粒 - 脂质共定位与细胞相互作用来证实结果。因此，我们的工作支持这样的观念：肺表面活性剂对吸入纳米颗粒起保护作用。因此，应考虑表面活性剂的作用在纳米颗粒毒性或药物纳米载体摄取的预测评估中。基于这项工作中介绍的模型可用于使用工程纳米颗粒进行临床前测试。
Pulmonary surfactant forms a sub-micrometer thick fluid layer that covers the surface of alveolar lumen and inhaled nanoparticles therefore come in to contact with surfactant prior to any interaction with epithelial cells. We investigate the role of the surfactant as a protective physical barrier by modeling the interactions using silica-Curosurf-alveolar epithelial cell system in vitro. Electron microscopy displays that the vesicles are preserved in the presence of nanoparticles while nanoparticle-lipid interaction leads to the formation of mixed aggregates. Fluorescence microscopy reveals that the surfactant decreases the uptake of nanoparticles by up to two orders of magnitude in two models of alveolar epithelial cells, A549 and NCI-H441, irrespective of immersed culture on glass or air-liquid interface culture on transwell. Confocal microscopy corroborates the results by showing nanoparticle-lipid colocalization interacting with the cells. Our work thus supports the idea that pulmonary surfactant plays a protective role against inhaled nanoparticles. The effect of surfactant should therefore be considered in predictive assessment of nanoparticle toxicity or drug nanocarrier uptake. Models based on the one presented in this work may be used for preclinical tests with engineered nanoparticles.
