title: Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells.
abstract: Inhaled nanoparticles (NPs) have high-deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona. Confocal live cell microscopy confirmed that Curosurf® lowered intracellular dissolution, thus delaying the onset of cell death compared to bare ZnONWs. Despite reducing dissolution, Curosurf® significantly increased the uptake of ZnONWs within TT1 cells, ultimately increasing their toxicity after 24 h. Although serum improved ZnONW dispersion in suspension similar to Curosurf®, it had no effect on ZnONW internalization and toxicity, indicating a unique role of PS in promoting particle uptake. In the absence of PS, ZnONW length had no effect on dissolution kinetics or degree of cellular toxicity, indicating a less important role of length in determining ZnONW bioreactivity. This work provides unique findings on the effects of PS on the stability and toxicity of ZnONWs, which could be important in the study of pulmonary toxicity and epithelial-endothelial translocation of nanoparticles in general.
authors.affiliation: a Department of Materials and London Centre for Nanotechnology , and.
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Theodorou
authors.affiliation: a Department of Materials and London Centre for Nanotechnology , and.|b National Heart and Lung Institute, Imperial College London , Exhibition Road , London , United Kingdom .
authors.forename: Pakatip
authors.initials: P
authors.lastname: Ruenraroengsak
authors.affiliation: c Department of Pharmacology and Toxicology , Rutgers University , Piscataway , NJ , USA .
authors.forename: Andrew
authors.initials: A
authors.lastname: Gow
authors.affiliation: d Department of Environmental and Occupational Health , Rutgers University, School of Public Health , Hoes LaneWest, Piscataway, NJ , USA , and.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schwander
authors.affiliation: e Nicholas School of the Environment and Duke Global Health Institute, Duke University , Durham , NC , USA.
authors.forename: Junfeng Jim
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: b National Heart and Lung Institute, Imperial College London , Exhibition Road , London , United Kingdom .
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: b National Heart and Lung Institute, Imperial College London , Exhibition Road , London , United Kingdom .
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: a Department of Materials and London Centre for Nanotechnology , and.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Ryan
authors.affiliation: a Department of Materials and London Centre for Nanotechnology , and.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Porter
mesh_terms: D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D053770:Nanowires / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D010743:Phospholipids / Q000494:pharmacology* / Q000502:physiology; D011650:Pulmonary Alveoli / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D012995:Solubility; D013499:Surface Properties; D013552:Swine; D015034:Zinc Oxide / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D001688:Biological Products; D010743:Phospholipids; D011663:Pulmonary Surfactants; C068291:poractant alfa; D015034:Zinc Oxide
keywords: Alveoli; Curosurf®; epithelial uptake; nanoparticles; nanotoxicity