title: Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation.
abstract: Nanoparticle (NP) pharmacokinetics and biological effects are influenced by many factors, especially surface physicochemical properties. We assessed the effects of an amorphous silica coating on the fate of zinc after intravenous (IV) injection of neutron activated uncoated (65)ZnO or silica-coated (65)ZnO NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for (65)Zn radioactivity. The protein coronas on each ZnO NP after incubation in rat plasma were analyzed by SDS-PAGE gel electrophoresis and mass spectrometry of selected gel bands. Plasma clearance for both NPs was biphasic with rapid initial and slower terminal clearance rates. Half-lives of plasma clearance of silica-coated (65)ZnO were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (65)ZnO (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (65)ZnO group had higher (65)Zn associated with red blood cells and higher initial uptake in the liver. The (65)Zn concentrations in all the other tissues were significantly lower in the silica-coated than uncoated groups. We also found that the protein corona formed on silica-coated ZnO NPs had higher amounts of plasma proteins, particularly albumin, transferrin, A1 inhibitor 3, α-2-hs-glycoprotein, apoprotein E and α-1 antitrypsin. Surface modification with amorphous silica alters the protein corona, agglomerate size, and zeta potential of ZnO NPs, which in turn influences ZnO biokinetic behavior in the circulation. This emphasizes the critical role of the protein corona in the biokinetics, toxicology and nanomedical applications of NPs.
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Nagarjun V
authors.initials: NV
authors.lastname: Konduru
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Murdaugh
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Swami
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Jimenez
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Donaghey
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
authors.affiliation: a Department of Environmental Health , Harvard T. H. Chan School of Public Health, Molecular and Integrative Physiological Sciences Program and Center for Nanotechnology and Nanotoxicology , Boston , MA , USA.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*; D000066970:Protein Corona / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000097:blood* / Q000737:chemistry*; D013499:Surface Properties; D015034:Zinc Oxide / Q000097:blood* / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D000066970:Protein Corona; D012822:Silicon Dioxide; D015034:Zinc Oxide
keywords: Biokinetics; nanoparticles; silica coating; surface chemistry; zinc radioisotope