Pulmonary surfactant inhibition of nanoparticle uptake by alveolar epithelial cells

TL;DR

This study demonstrates that pulmonary surfactant significantly reduces nanoparticle uptake by alveolar epithelial cells, highlighting its protective role and implications for nanoparticle toxicity assessment and drug delivery.

Contribution

The paper introduces an in vitro model showing how pulmonary surfactant inhibits nanoparticle uptake, providing insights into its protective mechanism in the lungs.

Findings

Surfactant decreases nanoparticle uptake by up to two orders of magnitude.

Nanoparticles form mixed aggregates with surfactant lipids.

Surfactant's protective effect is consistent across different cell models.

Abstract

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.