Calcium co-Localization with in vivo Cerium Phosphate Nanoparticle Formation after Intratracheal Instillation Dosing with CeCl3 or CeO2 NPs

The bioprocessing of CeO2 nanoparticles after uptake in lung tissues is compared with the formation of nanoparticles after inhalation of CeCl3 aerosols. In both cases, high-resolution TEM/STEM analyses indicate that cerium phosphate nanoparticles (NPs) had precipitated in phagolysosomal regions within macrophages. Importantly, the primary particle size, morphology, and agglomeration tendencies of the NPs were strikingly similar. Formation of cerium phosphate NPs after bioprocessing of inhaled CeO2 crystals proceeds via dissolution, ion transport, followed by nucleation and growth [1]. Application of 2D and 3D elemental maps of the NP bioprocessing stages and corresponding tissue interactions provide insights on the breakdown mechanisms, formation of new precipitates, size, and morphology changes of the original delivered NPs, and ion transport phenomena that result in secondary particle formation. Particle size and morphology are very similar for all of the cerium phosphate NPs, suggesting a common underlying precipitation mechanism independent of whether the metal ions are derived from dissolution of nanoparticles (CeO2) or from instilled metal ions (CeCl3).