Carbon Nanotube Biodegradation by Neutrophil Myeloperoxidase

Details

• Personal Author:
  Kagan VE ; Kim K ; Star A
• Description:
  Biopersistence of single- and multiwalled carbon nanotubes, graphene oxide (GO) and several other types of carbonaceous nanomaterials is an essential determinant of their health effects. In 2008, we have discovered (Nano Letters 8 (11), 3899-3903, 2008) that carbonaceous nanomaterials can be degraded by oxidative enzymes, such as peroxidases. Our extensive studies during the subsequent period - funded by this grant - have demonstrated that successful biodegradation is one of the major factors defining the life span and biological responses to nanoparticles. Our work in this area has been cited about 2,000 times and laid the foundation for a new field of nanotoxicology. Our detailed studies have revealed the role and contribution of different oxidative enzymes of inflammatory cells - myeloperoxidase, eosinophil peroxidase, lactoperoxidase, hemoglobin, and xanthine oxidase - to the reactions of nanoparticle biodegradation. We obtained essential results characterizing interactions of nanomaterials with hemoproteins dependent on the specific features of their physico-chemical and structural characteristics. Mechanistically, we deciphered the significance of immobilized peroxidase reactive intermediates vs diffusible small molecule oxidants (hypochlorous and hypobromous acids) for the overall oxidative biodegradation process in neutrophils and eosinophils. We also deciphered the peroxynitrite-driven pathways realized in macrophages via the engagement of NADPH oxidase- and NO synthase-triggered oxidative mechanisms. We established the importance of genetic factors and their manipulations for the enzymatic biodegradation in vivo. We documented possible involvement of oxidative machinery of other professional phagocytes such as microglial cells, myeloid-derived suppressor cells, in the context of biodegradation relevant to targeted drug delivery. Finally, we described a novel type of biodegradation realized via the activation of the "dormant" peroxidase activity of hemoproteins by nano-surfaces. Overall, our studies pave the way to developing new strategies for creating safe by design carbonaceous nanoparticles with optimized characteristics regulatable life-span in circulation. [Description provided by NIOSH]
• Subjects:
  Blood Enzymes Immune System Macrophages Occupational Health Oxidants Safety Toxicology
• Keywords:
  Biodegradation Biological Effects Carbon Nanotubes CNT Enzyme Activity Genetic Factors Graphene Oxide Immune Reaction Nanomaterials Nanoparticles Nanotoxicology Oxidative Processes Peroxidases Phagocytic Activity

  More +
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-37
• NIOSHTIC Number:
  nn:20053278
• NTIS Accession Number:
  PB2019-100250
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-008282, 2016 Oct; :1-37
• Contact Point Address:
  Valerian E. Kagan, PhD, DSc, University of Pittsburgh, 100 Technology Drive, Bridgeside Point, Room 330, Pittsburgh, PA 15219-3138
• Email:
  kagan@pitt.edu
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:035b0cf65b5a0b4a962c8c219a0f0cfbfe0f601bfdd9ee9692b23db0c0da36689ee9e334c335a9bf6a59daa5cd5d3a1cace1cf0b0f1206b5b4c81cb2648c9cbe
• Download URL:
  https://stacks.cdc.gov/view/cdc/218761/cdc_218761_DS1.pdf
• File Type:
  [PDF - 297.64 KB ]