title: Nanoparticles in the lung and their protein corona: the few proteins that count.
abstract: The formation of protein coronae on nanoparticles (NPs) has been investigated almost exclusively in serum, despite the prevailing route of exposure being inhalation of airborne particles. In addition, an increasing number of nanomedicines, that exploit the airways as the site of delivery, are undergoing medical trials. An understanding of the effects of NPs on the airways is therefore required. To further this field, we have described the corona formed on polystyrene (PS) particles with different surface modifications and on titanium dioxide particles when incubated in human bronchoalveolar lavage fluid (BALF) from patients with pulmonary alveolar proteinosis (PAP). We show, using high-resolution quantitative mass spectrometry (MS(E)), that a large number of proteins bind with low copy numbers but that a few "core" proteins bind to all particles tested with high fidelity, averaging the surface properties of the different particles independent of the surface properties of the specific particle. The averaging effect at the particle surface means that differing cellular effects may not be due to the protein corona but due to the surface properties of the nanoparticle once inside the cell. Finally, the adherence of surfactant associated proteins (SP-A, B and D) suggests that there may be interactions with lipids and pulmonary surfactant (PSf), which could have potential in vivo health effects for people with chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), or those who have increased susceptibility toward other respiratory diseases.
authors.affiliation: a Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital , Southampton , UK .|b Institute for Life Sciences, University of Southampton , Southampton , UK .
authors.forename: Harry
authors.initials: H
authors.lastname: Whitwell
authors.affiliation: a Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital , Southampton , UK .
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Mackay
authors.affiliation: c School of Geography, Earth and Environmental Sciences, University of Birmingham , Birmingham , UK .
authors.forename: Christine
authors.initials: C
authors.lastname: Elgy
authors.affiliation: d Leukocyte Biology, Royal Brompton Campus, Imperial College London , London , UK , and.
authors.forename: Cliff
authors.initials: C
authors.lastname: Morgan
authors.affiliation: d Leukocyte Biology, Royal Brompton Campus, Imperial College London , London , UK , and.
authors.forename: Mark
authors.initials: M
authors.lastname: Griffiths
authors.affiliation: a Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital , Southampton , UK .|b Institute for Life Sciences, University of Southampton , Southampton , UK .|e National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Howard
authors.initials: H
authors.lastname: Clark
authors.affiliation: b Institute for Life Sciences, University of Southampton , Southampton , UK .|e National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Skipp
authors.affiliation: a Child Health, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital , Southampton , UK .|b Institute for Life Sciences, University of Southampton , Southampton , UK .|e National Institute for Health Research, Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research, University Hospital Southampton NHS Foundation Trust , Southampton , UK.
authors.forename: Jens
authors.initials: J
authors.lastname: Madsen
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D011137:Polystyrenes / Q000737:chemistry / Q000633:toxicity*; D000066970:Protein Corona / Q000378:metabolism*; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D011137:Polystyrenes; D000066970:Protein Corona; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C009495:titanium dioxide; D014025:Titanium
keywords: Corona; lung; nanoparticles; surface chemistry; surfactant