The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnology. Inhaled NPs can deposit in the deep lung at which interacting with the pulmonary surfactant (PS). The PS is a detergent-like lipid-protein biofluid that is responsible for the first-line host defense and for reducing the alveolar surface tension. Interaction with the PS represents the initial nano-bio interaction in the lung, which also determines the fate of inhaled NPs and their potential therapeutic or toxicological effect. Despite the increasing study of nano-bio interactions, detailed molecular mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using combined in vitro and in silico methods, we show how physicochemical properties and aggregation states of the NPs regulate their interactions with the PS film. We have developed a novel analytical method called the constrained drop surfactometry (CDS). We show that the CDS can be used as a high-fidelity biophysical model for simulating interactions between airborne NPs and natural PS. Our study supports a novel concept of the PS corona acquired by all NPs entering human body via the respiratory portal, as a counterpart of the protein corona for NPs entering the blood vessel. It is the physicochemical property of the PS corona, rather than that of the pristine NPs, that determines the biological identity of the inhaled NPs and their subsequent interactions with cells and other biological entities. Our studies shed light on understanding the toxicity of inhaled NPs and better design of nanocarriers for pulmonary drug delivery. Our results also raise a caveat that all studies of inhalation nanotoxicology and NP-based pulmonary drug delivery should consider the influence of the PS corona.

Pulmonary surfactant corona and nano-bio interactions in the lung

2019 Fall National Meeting

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