The Differential Toxicity of Three Different Oxidized Nickel Compound Nanoparticles and the Effects of Particle Surface Ligands in Mouse Alveolar Macrophages

Details

• Personal Author:
  Kendall, Rebekah L. ; Hamilton, Raymond F. Jr. ; Albright, Jacob M. ; Zhao, Yu ; Hang, Yingjie ; Tang, Chaoyun ; Porter, Dale W. ; Wu, Nianqiang ; Holian, Andrij
• Description:
  Nickel-compound engineered nanomaterials (Ni-X NP) have diverse applications, yet their continued use raises concerns for potential health impacts upon exposure. This study investigated 3 structurally distinct Ni-X-NP-pure NiO (NCZ), NiO@Ni(OH)2 (SIG), and Ni@NiO@Ni(OH)2 (AA)-to determine how core composition and surface functionalization contribute to bioactivity. Each Ni-X NP was modified with surface moieties (-OH, -COOH, and -CH3) to assess the efficacy of surface modifications in reducing bioactivity. Ni-X NP were thoroughly characterized for structure, surface chemistry, and Ni2+ ion release in simulated lysosomal fluid. Red blood cells (RBCs) were used to evaluate the hemolytic capabilities of the nanoparticles, and primary murine alveolar macrophages (AM), and murine ex vivo alveolar macrophages (mexAM) were used to assess uptake, cytotoxicity, IL-1β release, and lysosomal membrane permeability (LMP). Results showed that NiO@Ni(OH)2 nanoparticles induced the greatest hemolysis in RBC, elicited the greatest IL-1β response in AM and mexAM, and produced the most LMP in mexAM. The Ni@NiO@Ni(OH)2 nanoparticle released the most Ni2+ and caused profound reductions in AM cell viability but failed to cause RBC hemolysis or LMP. Pure NiO nanoparticles exhibited minimal bioactivity and low Ni2+ release. Surface modification with (-COOH) or (-CH3) effectively reduced bioactivity in LMP-mediated inflammation but had minimal effect on Ni2+-driven toxicity. This study reveals that Ni-X NP bioactivity depends on both core composition and surface chemistry, and that surface functionalization reduces inflammation only when lysosomal damage is the primary driver. These findings underscore the need for careful design and evaluation of engineered nanomaterials.
• Subjects:
  Hazardous Substances Mice Nanoparticles Nickel Occupational Health Safety
• Keywords:
  Author Keywords: Nanoparticle; Nickel Compound; Nickel Oxide; Macrophage; LMP Nickel Compounds; Nanomaterials; Nanoparticles; Toxicology; Cytotoxicity; Macrophages; Nickel Oxide;
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Montana ; Massachusetts ; West Virginia ; Boston Region [OSHA] ; Denver Region [OSHA] ; Philadelphia Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  15 pdf pages
• Volume:
  208
• Issue:
  2
• NIOSHTIC Number:
  nn:20071123
• Citation:
  Toxicol Sci 2025 Dec; 208(2):369-383
• Email:
  becky.kendall@mso.umt.edu
• CAS Registry Number:
  Nickel (CAS RN 7440-02-0) ; Nickel monoxide (CAS RN 1313-99-1)
• Federal Fiscal Year:
  2026
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a15185672ea41475802a333a40185c6002a188515f0d1632457147a220c2c3342f290c0dbb3253f533f522e199609dbc99e4d6593f043af8df19ec6f50d371e0
• Download URL:
  https://stacks.cdc.gov/view/cdc/257899/cdc_257899_DS1.pdf
• File Type:
  [PDF - 2.49 MB ]