Abstract

BackgroundWe previously showed that cerium oxide (CeO2), barium sulfate (BaSO4) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats. We hypothesize that these NPs acquire coronas with different protein compositions that may influence their clearance from the lungs.MethodsCeO2, silica-coated CeO2, BaSO4, and ZnO NPs were incubated in rat lung lining fluid in vitro. Then, gel electrophoresis followed by quantitative mass spectrometry was used to characterize the adsorbed proteins stripped from these NPs. We also measured uptake of instilled NPs by alveolar macrophages (AMs) in rat lungs using electron microscopy. Finally, we tested whether coating of gold NPs with albumin would alter their lung clearance in rats.ResultsWe found that the amounts of nine proteins in the coronas formed on the four NPs varied significantly. The amounts of albumin, transferrin and α-1 antitrypsin were greater in the coronas of BaSO4 and ZnO than that of the two CeO2 NPs. The uptake of BaSO4 in AMs was less than CeO2 and silica-coated CeO2 NPs. No identifiable ZnO NPs were observed in AMs. Gold NPs coated with albumin or citrate instilled into the lungs of rats acquired the similar protein coronas and were cleared from the lungs to the same extent.ConclusionsWe show that different NPs variably adsorb proteins from the lung lining fluid. The amount of albumin in the NP corona varies as does NP uptake by AMs. However, albumin coating does not affect the translocation of gold NPs across the air-blood barrier. A more extensive database of corona composition of a diverse NP library will develop a platform to help predict the effects and biokinetics of inhaled NPs.

Highlights

  • We previously showed that cerium oxide (CeO2), barium sulfate (BaSO4) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats

  • The hydrodynamic diameter of NP suspensions in DI and zeta potentials were measured before incubation in harvested cell-free rat bronchoalveolar lavage fluid (BALf) for 30 min at 37 °C by dynamic light scattering (DLS) using a Malvern ZetaSizer Nano (Westborough, MA)

  • The zeta potentials of CeO2 and ZnO NPs changed from positive to negative, and the hydrodynamic diameters of all NPs increased after incubation in BALf

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Summary

Introduction

We previously showed that cerium oxide (CeO2), barium sulfate (BaSO4) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats. We hypothesize that these NPs acquire coronas with different protein compositions that may influence their clearance from the lungs. Corona formation takes place in the alveolar lining fluid. It consists of plasma proteins, a surface-active phospholipid (PL)-protein mixture, known as pulmonary surfactant, and a thin layer of aqueous hypophase especially in the alveolar “corners” [9]. SP-A and SP-D opsonize inhaled microbes, allergens, and other foreign bodies such as NPs to varying degrees, and promote their recognition, ingestion and dissolution by resident alveolar macrophages (AMs) and other leukocytes [11, 12]

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