Simulated Biological Fluid Exposure Changes Nanoceria’s Surface Properties but not its Biological Response

Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria’s surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria’s surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria’s surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates

Cerium dioxide, a Jekyll and Hyde nanomaterial, can increase basal and decrease elevated inflammation and oxidative stress

It was hypothesized that the catalyst nanoceria can increase oxidative stress/inflammation from the basal state and reduce it from the elevated state . Nanoceria are cleared by macrophages. To test the hypothesis, M0 (non-polarized), M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated, regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Responses were quantified by arginase activity, IL-1ß level, cell oxygen consumption rate (OCR), the glycolysis stress test (GST), morphology determined by light microscopy, macrophage phenotype marker expression and morphology using a novel three dimensional immunohistochemical method, and RT-qPCR. Nanoceria blocked arginase and IL-1ß effects, increased M0 cell OCR and GST toward the M2 phenotype and altered multiple M1- and M2-like cell endpoints toward the M0 level. M1-like cells had greater volume and less circularity/roundness, and the M2-like cells had greater volume than M0 macrophages. Nanoceria converted M1- and M2-like cells toward M0 morphology. The results are overall consistent with the hypothesis