Interaction with the pulmonary surfactant film, the first line of host defense in the lungs, represents the initial nano-bio interaction following inhalation. This interaction determines the fate of inhaled nanoparticles and their potential therapeutic or toxicological effects. Despite considerable progress in optimizing the physicochemical properties of nanoparticles for enhanced delivery and targeting, the mechanisms governing their interactions with the pulmonary surfactant film remain poorly understood. We have investigated the interaction mechanisms between natural pulmonary surfactant and a broad spectrum of particulate matter, including engineered nanoparticles, carbonaceous nanomaterials, environmental PM2.5, e-cigarette aerosols, and micro-/nanoplastics.
Schematic illustration of micro/nanoplastic-induced lung injury. The left-half of the schematic shows a normal alveolus. The pulmonary surfactant, synthesized by the alveolar type II epithelial cells, covers the entire air–water surface of the alveolus, in the form of a multilayered phospholipid film stabilized by surfactant-associated proteins. The right-half of the schematic shows the injured alveolus due to particulate insults. Alveolar macrophages secrete cytokines, such as interleukin (IL)-6. Immune cells, such as neutrophils, eosinophils (not shown), and dendritic cells (not shown), are recruited to the alveolar space. Nanoplastics form heteroaggregation with the pulmonary surfactant film at the alveolar–capillary interface, thus inhibiting the biophysical function of pulmonary surfactant (Xu et al. 2023, Environ. Sci. Technol. 57:21050).
Qualitative phase diagram to predict the hazardous potential of the flavoring chemicals used in e-cigarette products. The three corners of the phase diagram represent carbonyl, aromatic, and hydroxyl groups of the flavoring chemicals. It suggests that esters, possessing only a carbonyl group, such as ethyl acetate and ethyl butyrate, have the least adverse biophysical impact on pulmonary surfactant. Aldehydes, such as maltol and ethyl maltol, and heterocycles, such as vanillin and ethyl vanillin, which are composed of aromatic, hydroxyl, and carbonyl groups, demonstrate a moderate inhibitory effect on pulmonary surfactant. Aromatic compounds with a hydroxyl group, such as menthol and benzyl alcohol, have the highest adverse impact. The biophysical impact and surfactant inhibition were determined by the increase in surface tension and level of disturbance to the surfactant film (Goros et al. 2023, Environ. Sci. Technol. 57:15882).
We have employed molecular dynamics (MD) simulations to study the formation of pulmonary surfactant biomolecular coronas on nanoparticles and the interactions of nanoparticles with varying physicochemical properties with pulmonary surfactant films. These studies provide novel molecular-level insights into nano–bio interactions at the pulmonary interface and advance mechanistic understanding of the pulmonary toxicity of inhaled nanoparticles. Our findings suggest that both pulmonary nanotoxicology and nanoparticle-based pulmonary drug delivery should explicitly consider the formation and biological implications of the pulmonary surfactant biomolecular corona.
Biomolecular corona formed on a silver nanoparticle (Hu et al. 2017, ACS Nano 11:6832 ).
Biomolecular corona formed on a polystyrene nanoparticle (Hu et al. 2017, ACS Nano 11:6832 ).
A hydrophilic anionic nanoparticle interacting with a surfactant film (Hu et al. 2013, ACS Nano 7:10525).
A hydrophobic anionic nanoparticle interacting with a surfactant film (Hu et al. 2013, ACS Nano 7:10525).
Xu X, Goros RA, Dong Z, Meng X, Li G, Chen W, Liu S, Ma J, Zuo YY*, Microplastics and nanoplastics impair the biophysical function of pulmonary surfactant by forming heteroaggregates at the alveolar-capillary interface, Environ. Sci. Technol. 57 (2023) 21050-21060. PDF
Goros RA, Xu X, Li G, Zuo YY*, Adverse biophysical impact of e-cigarette flavors on pulmonary surfactant, Environ. Sci. Technol. 57 (2023) 15882-15891. PDF
Xu L, Yang Y, Simien JM, Kang C, Li G, Xu X, Haglund E, Sun R, Zuo YY*, Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant. Am. J. Physiol. Lung Cell Mol. Physiol. 323 (2022) L165-L177. (Editor’s Choice: APSselect) PDF
Yang Y, Xu L, Dekkers S, Zhang LG, Cassee FR, ZuoYY*, Aggregation state of metal-based nanomaterials at the pulmonary surfactant film determines biophysical inhibition. Environ. Sci. Technol. 52 (2018) 8920-8929. PDF
Yang Y, Wu Y, Ren Q, Zhang LG, Liu S, Zuo YY*, Biophysical assessment of pulmonary surfactant predicts the lung toxicity of nanomaterials. Small Methods 2 (2018) 1700367. PDF
Hu Q, Bai X, Hu G, and Zuo YY*, Unveiling the molecular structure of pulmonary surfactant corona on nanoparticles, ACS Nano 11 (2017) 6832-6842. PDF
Valle RP, Wu T, Zuo YY*, Biophysical influence of airborne carbon nanomaterials on nature pulmonary surfactant. ACS Nano 9 (2015) 5413-5421. PDF
Valle RP, Huang CL, Loo JSC, Zuo YY*, Increasing hydrophobicity of nanoparticles intensifies lung surfactant film inhibition and particle retention, ACS Sustainable Chem. & Eng. 2 (2014) 1574-1580. PDF
Hu G, Jiao B, Shi X, Valle RP, Fan Q, Zuo YY*, Physicochemical properties of nanoparticles regulate translocation across pulmonary surfactant monolayer and formation of lipoprotein corona. ACS Nano 7 (2013) 10525-10533. PDF
Fan Q, Wang YE, Zhao X, Loo JSC, Zuo YY*, Adverse biophysical effects of hydroxyapatite nanoparticles on natural pulmonary surfactant, ACS Nano 5 (2011) 6410-6416. PDF