Calcium Co-Localization with In Vivo Cerium Phosphate Nanoparticle Formation After Intratracheal Instillation Dosing with CeCl3 or CeO2 NPs

Details

• Personal Author:
  Birch, M. Eileen ; Brain JD ; Dozier, Alan K. ; Drummy L ; Fernback, Joseph E. ; Graham UM ; Konduru NV ; Mahalingam K ; Molina RM ; Oberdorster G ; Wang C ; Birch, M. Eileen ; Brain JD ; Dozier, Alan K. ; Drummy L ; Fernback, Joseph E. ; Graham UM ; Konduru NV ; Mahalingam K ; Molina RM ; Oberdorster G ; Wang C
• Description:
  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. 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). In the lungs, bioprocessing of CeO2 and CeCl3 resulted in the formation of rod-shaped, aligned particles that were identified in EELS and EDS analyses as cerium phosphate. Surprisingly, elemental analyses also reveal for the first time, and with excellent reproducibility, the presence of Ca in the same localities as the in vivo precipitated cerium phosphate NPs. What controls the preferential coprecipitation, or what underlying pathways control the localized Ca enrichment are questions to be answered. Lung tissue samples were fixed by vascular perfusion with 2.5% glutaraldehyde, 2% paraformaldehyde in 0.1M HEPES buffer. The samples were processed for electron microscopy at 2 hours, 7 days, and 4 weeks post-instillation. High resolution imaging revealed that NPs formed at all of the selected timepoints and were located in lysosomal regions, along membrane surfaces, and inside mitochondria. The NPs had formed in a narrow particle size range (approximately 1-5 nm) and were bundled together in 3D-agglomerates that ranged up to several hundred nm. At high magnification, the individual nanoparticles tended to self-align into rod-shaped structures. [Description provided by NIOSH]
• Subjects:
  Aerosols Lung Occupational Health Particulate Matter Respiratory System Safety
• Keywords:
  3D Calcium Inhalation Lung Tissue Morphology Nanoparticles Nanotechnology Particle Size Sampling Three Dimensional
• ISSN:
  1431-9276
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  Massachusetts ; New York ; Ohio ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology ; DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• NIOSHTIC Number:
  nn:20050384
• Citation:
  Microsc Microanal 2017 Sep; 23(Suppl 1):1344-1345
• CAS Registry Number:
  Calcium (CAS RN 7440-70-2) ; Cerium phosphate (CAS RN 13454-71-2) ; Calcium (CAS RN 7440-70-2) ; Cerium phosphate (CAS RN 13454-71-2)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Microscopy and Microanalysis
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7be2d9adcc1ba1b892059fbb3c5f0f29a2925a109cc5a204fe98f7b2ede5e1bb6a083d7df8fb52331c115b4a26261573ab4237e255499bbda6d9d62914fb6cbf
• Download URL:
  https://stacks.cdc.gov/view/cdc/210754/cdc_210754_DS1.pdf
• File Type:
  [PDF - 418.14 KB ]