  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.
