Surface modification of zinc oxide nanoparticles with amorphous silica alters their fate in the circulation

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 (ZnO)-Zn-65 or silica-coated (ZnO)-Zn-65 NPs in male Wistar Han rats. Groups of IV-injected rats were sequentially euthanized, and 18 tissues were collected and analyzed for Zn-65 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 (ZnO)-Zn-65 were shorter (initial - <1 min; terminal - 2.5 min) than uncoated (ZnO)-Zn-65 (initial - 1.9 min; terminal - 38 min). Interestingly, the silica-coated (ZnO)-Zn-65 group had higher Zn-65 associated with red blood cells and higher initial uptake in the liver. The Zn-65 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, alpha-2-hs-glycoprotein, apoprotein E and alpha-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.