title: Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid.
abstract: When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles.
  
  
  BACKGROUND
  Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics.
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College, LondonUK. Electronic address: abhinav.kumar@kcl.ac.uk.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kumar
authors.affiliation: MRC-PHE Centre for Environment and Health and NIHR-HPRU in the Health Impact of Environmental Hazards, Environmental and Analytical Research, Division, Faculty of Life Sciences and Medicine, King's College, London, UK.
authors.forename: Elif Melis
authors.initials: EM
authors.lastname: Bicer
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College, LondonUK.
authors.forename: Anna Babin
authors.initials: AB
authors.lastname: Morgan
authors.affiliation: MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Faculty of Life Sciences and Medicine, King's College, London, UK.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Pfeffer
authors.affiliation: Centre for BioNano Interactions, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Marco
authors.initials: M
authors.lastname: Monopoli
authors.affiliation: Centre for BioNano Interactions, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Sweden.
authors.forename: Jonny
authors.initials: J
authors.lastname: Eriksson
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Edwards
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, Faculty of Life Sciences and Medicine, King's College, London, UK.
authors.forename: Steven
authors.initials: S
authors.lastname: Lynham
authors.affiliation: Genomics Centre, Faculty of Life Sciences and Medicine, King's College, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Annelie F
authors.initials: AF
authors.lastname: Behndig
authors.affiliation: Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.affiliation: GSK Medicines Research Centre, Stevenage, Hertfordshire, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Somers
authors.affiliation: GSK Medicines Research Centre, Stevenage, Hertfordshire, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Hassall
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College, LondonUK.
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College, LondonUK.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
authors.affiliation: MRC-PHE Centre for Environment and Health and NIHR-HPRU in the Health Impact of Environmental Hazards, Environmental and Analytical Research, Division, Faculty of Life Sciences and Medicine, King's College, London, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Mudway
mesh_terms: D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000302:isolation & purification; D001826:Body Fluids / Q000378:metabolism; D015922:Complement C1q / Q000096:biosynthesis / Q000302:isolation & purification; D003176:Complement C3 / Q000096:biosynthesis / Q000302:isolation & purification; D016503:Drug Delivery Systems; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D000066970:Protein Corona; D040901:Proteomics; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis / Q000302:isolation & purification; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D003176:Complement C3; D000066970:Protein Corona; D037662:Pulmonary Surfactant-Associated Protein A; D012822:Silicon Dioxide; D015922:Complement C1q; D016282:Aspartic Acid Endopeptidases; C498549:NAPSA protein, human
keywords: Nanoparticle; Plasma; Poly(vinyl) acetate; Protein corona; Proteomics; Respiratory tract lining fluid; Silica