title: Silica coating influences the corona and biokinetics of cerium oxide nanoparticles.
abstract: BACKGROUND
  The physicochemical properties of nanoparticles (NPs) influence their biological outcomes.
  
  
  METHODS
  We assessed the effects of an amorphous silica coating on the pharmacokinetics and pulmonary effects of CeO2 NPs following intratracheal (IT) instillation, gavage and intravenous injection in rats. Uncoated and silica-coated CeO2 NPs were generated by flame spray pyrolysis and later neutron-activated. These radioactive NPs were IT-instilled, gavaged, or intravenously (IV) injected in rats. Animals were analyzed over 28 days post-IT, 7 days post-gavage and 2 days post-injection.
  
  
  RESULTS
  Our data indicate that silica coating caused more but transient lung inflammation compared to uncoated CeO2. The transient inflammation of silica-coated CeO2 was accompanied by its enhanced clearance. Then, from 7 to 28 days, clearance was similar although significantly more (141)Ce from silica-coated (35%) was cleared than from uncoated (19%) (141)CeO2 in 28 days. The protein coronas of the two NPs were significantly different when they were incubated with alveolar lining fluid. Despite more rapid clearance from the lungs, the extrapulmonary (141)Ce from silica-coated (141)CeO2 was still minimal (<1%) although lower than from uncoated (141)CeO2 NPs. Post-gavage, nearly 100% of both NPs were excreted in the feces consistent with very low gut absorption. Both IV-injected (141)CeO2 NP types were primarily retained in the liver and spleen. The silica coating significantly altered the plasma protein corona composition and enhanced retention of (141)Ce in other organs except the liver.
  
  
  CONCLUSIONS
  We conclude that silica coating of nanoceria alters the biodistribution of cerium likely due to modifications in protein corona formation after IT and IV administration.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Nagarjun V
authors.initials: NV
authors.lastname: Konduru
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Jimenez
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Swami
authors.affiliation: National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Friend
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, P.O. Box 9530, Morgantown, WV, 26506, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. rmolina@hsph.harvard.edu.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
mesh_terms: D000818:Animals; D002563:Cerium / Q000737:chemistry*; D007700:Kinetics; D053768:Metal Nanoparticles; D008854:Microscopy, Electron; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D002563:Cerium; C030583:ceric oxide; D012822:Silicon Dioxide