title: Proinflammatory Effects of Pyrogenic and Precipitated Amorphous Silica Nanoparticles in Innate Immunity Cells.
abstract: Amorphous silica nanoparticles (ASNP) can be synthetized via several processes, 2 of which are the thermal route (to yield pyrogenic silica) and the wet route from a solution containing silicate salts (to obtain precipitated, colloidal, mesoporous silica, or silica gel). Both methods of synthesis lead to ASNP that are applied as food additive (E551). Current food regulation does not require that production methods of additives are indicated on the product label, and, thus, the ASNP are listed without mentioning the production method. Recent results indicate, however, that pyrogenic ASNP are more cytotoxic than ASNP synthesized through the wet route. The present study was aimed at clarifying if 2 representative preparations of ASNP, NM-203 (pyrogenic) and NM-200 (precipitated), of comparable size, specific surface area, surface charge, and hydrodynamic radius in complete growth medium, had different effects on 2 murine macrophage cell lines (MH-S and RAW264.7 cells). Our results show that, when incubated in protein-rich fluids, NM-203 adsorbed on their surface more proteins than NM-200 and, once incubated with macrophages, elicited a greater oxidative stress, assessed from Hmox1 induction and ROS production. Flow cytometry and helium ion microscopy indicated that pyrogenic NM-203 interacted with macrophages more strongly than the precipitated NM-200 and triggered a more evident inflammatory response, evaluated with Nos2 induction, NO production and the secretion of TNF-α, IL-6 and IL-1β. Moreover, both ASNP synergized macrophage activation by bacterial lipopolysaccharide (LPS), with a higher effect observed for NM-203. In conclusion, the results presented here demonstrate that, compared to precipitated, pyrogenic ASNP exhibit enhanced interaction with serum proteins and cell membrane, and cause a larger oxidative stress and stronger proinflammatory effects in macrophages. Therefore, these 2 nanomaterials should not be considered biologically equivalent.
authors.affiliation: *Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; School of Medicine and.
authors.forename: Luisana
authors.initials: L
authors.lastname: Di Cristo
authors.affiliation: School of Medicine and AMBER centre (CRANN Institute), Trinity College Dublin, Dublin, Ireland;
authors.forename: Dania
authors.initials: D
authors.lastname: Movia
authors.affiliation: *Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy;
authors.forename: Massimiliano G
authors.initials: MG
authors.lastname: Bianchi
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy;
authors.forename: Manfredi
authors.initials: M
authors.lastname: Allegri
authors.affiliation: School of Medicine and.
authors.forename: Bashir M
authors.initials: BM
authors.lastname: Mohamed
authors.affiliation: Advanced Microscopy Laboratory, Trinity College Dublin, Dublin, Ireland;
authors.forename: Alan P
authors.initials: AP
authors.lastname: Bell
authors.affiliation: School of Medicine and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moore
authors.affiliation: *Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy;
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.affiliation: Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Rasmussen
authors.affiliation: Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy.
authors.forename: Juan
authors.initials: J
authors.lastname: Riego-Sintes
authors.affiliation: School of Medicine and AMBER centre (CRANN Institute), Trinity College Dublin, Dublin, Ireland;
authors.forename: Adriele
authors.initials: A
authors.lastname: Prina-Mello
authors.affiliation: Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy; ovidio.bussolati@unipr.it.
authors.forename: Ovidio
authors.initials: O
authors.lastname: Bussolati
authors.affiliation: *Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy;
authors.forename: Enrico
authors.initials: E
authors.lastname: Bergamaschi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D011232:Chemical Precipitation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D036103:Nanotechnology / Q000379:methods; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013499:Surface Properties
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D012822:Silicon Dioxide
keywords: amorphous silica nanoparticles; food additive; inflammation; macrophages; oxidative stress; protein corona