Nanoceria Dissolution and Carboxylic Acid Stabilization in Aqueous Dispersions

Abstract

The objective was to determine whether carboxylic acids stabilize nanoceria in aqueous dispersions. Citric acid is used as a stabilizing agent for hydrothermal syntheses of nanoceria and for nanoceria dispersions. Nanoceria has been shown to have therapeutic potential for conditions with an oxidative stress/inflammation component including cancer, radiation damage, bacterial infection, sepsis, wounds, stroke‐induced ischemia, and retinal degeneration. It is used as an abrasive to prepare integrated circuits by chemical mechanical planarization and as a combustion catalyst in diesel fuel. Citrate‐coated nanoceria (average primary particle size ~ 4 nm (determined by electron microscopy; EM), hydrodynamic diameter of agglomerates in aqueous dispersions ~ 14 nm (determined by dynamic light scattering; DLS)) was incubated in multiple media for months. Nanoceria was introduced into 2 kD MWCO Slide‐A‐LyzerTM dialysis cassettes immersed in ~ 300 mOsm/L media. Samples from within and outside of the cassette were withdrawn for cerium quantitation by inductively coupled plasma mass spectrometry and high resolution electron microscopy (HR‐EM). Cerium quantitation, hydrodynamic diameter determination, and electron microscopic observations were repeatedly conducted. Nanoceria dissolution occurred at pH 4.5, shown by increased cerium in media surrounding the dialysis cassette and decreased primary particle size (1 to 3 nm, HR‐EM) within the cassette. Nanoceria agglomerates were ~ 10 to 15 nm in the presence of citric and malic acids and ammonium but grew to ~ 1 micron in media containing acetic, glutaric, tricarballylic, 3‐hydroxybutyric, adipic, or pimelic acid. In medium containing citrate, the nanoceria primary particle core retained its crystalline structure. Dissolution occurred at the nanoceria particle surface, which was rich in Ce(III); the antioxidant valence state. Cerium‐containing agglomerates (~ 10 nm comprised of 1 to 3 nm primary particles) were seen in the citric acid medium surrounding the dialysis cassette, suggesting diffusion of cerium through the dialysis cassette membrane followed by particle formation in the medium. In contrast, appreciable nanoceria dissolution did not occur in the presence of horseradish peroxidase and hydrogen peroxide at pH 6.2, a condition shown to degrade carbon nanotubes. By extension of the observations in acidic media, acidic environments, as found in phagolysosomes, may degrade nanoceria by dissolution. Carboxylic acids are known to form coordination complexes with metal ions. Formation of cerium‐chelate complexes after nanoceria dissolution may enable cerium redistribution within animals and uptake into plant roots. Ligands that can enable nanoceria dissolution in acidic environments greatly affect nanoceria's fate (dissolution rate and size).Support or Funding Information1R01GM109195