title: Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties.
abstract: BACKGROUND
  Silica (SiO₂) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems.
  
  
  OBJECTIVE
  To assess the potential impact of SiO₂ NP exposure and NPs chemical modifications in allergic airway inflammation.
  
  
  METHODS
  Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO₂ NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue.
  
  
  RESULTS
  Plain SiO₂ NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO₂ NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis.
  
  
  CONCLUSIONS
  Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO₂ NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans.
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Viviana
authors.initials: V
authors.lastname: Marzaioli
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München (TUM) and German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Aguilar-Pimentel
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weichenmeier
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Luxenhofer
authors.affiliation: IBE R&D gGmbH, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wiemann
authors.affiliation: BASF, Ludwigshafen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.affiliation: BASF, Ludwigshafen, Germany.
authors.forename: Wendel
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: Bayer Technology Services, Leverkusen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eiden
authors.affiliation: Department of Dermatology, Venereology and Allergology, Universitätsmedizin Göttingen (UMG), Göttingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt-Weber
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany ; Department of Dermatology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Gutermuth
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Alessandrini
mesh_terms: D000818:Animals; D005260:Female; D007155:Immunologic Factors / Q000633:toxicity*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology* / Q000517:prevention & control; D012822:Silicon Dioxide / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D007155:Immunologic Factors; D012822:Silicon Dioxide
keywords: allergic inflammation; health impact; immunomodulation