Biophysical Assessment of Pulmonary Surfactant Predicts the Lung Toxicity of Nanomaterials

Abstract With the rapid development of nanotechnology and an increasing use of nanoenabled consumer products, there is an urgent need to develop precautionary tools to evaluate acute lung toxicity of engineered nanomaterials (ENMs). As natural pulmonary surfactant (PS) film represents the initial barrier of nano–bio interactions in the lungs, a novel in vitro experimental method, called constrained drop surfactometry (CDS), is developed to quantitatively evaluate PS inhibition caused by ENMs. The results show that at a very low concentration, four representative ENMs, including carbon nanotubes, graphene oxide, zinc oxide, and silver nanoparticles, all increase in vitro minimum surface tension of a modified natural PS, Infasurf. These in vitro results are related to the extensive alveolar collapse and inflammation observed in vivo in mice exposed to these ENMs in an intratracheal instillation model. Thus, there may be a direct correlation between in vitro surface tension increase due to PS inhibition by ENMs and in vivo lung toxicity revealed by alveolar collapse and inflammation. Compared to commonly used animal models, CDS holds great promise for the development of an animal‐free, easy‐to‐use, and low‐cost precautionary assay for the prediction of acute lung toxicity of inhaled ENMs.