Enzymatic Oxidative Biodegradation of Nanoparticles: Mechanisms, Significance and Applications

Details

• Alternative Title:
  Toxicol Appl Pharmacol
• Personal Author:
  Vlasova, Irina I. ; Kapralov, Alexandr A. ; Michael, Zachary P. ; Burkert, Seth C. ; Shurin, Michael R. ; Star, Alexander ; Shvedova, Anna A. ; Kagan, Valerian E.
• Description:
  Biopersistence of carbon nanotubes, graphene oxide (GO) and several other types of carbonaceous nanomaterials is an essential determinant of their health effects. Successful biodegradation is one of the major factors defining the life span and biological responses to nanoparticles. Here, we review 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 further focus on interactions of nanomaterials with hemoproteins dependent on the specific features of their physico-chemical and structural characteristics. Mechanistically, we highlight 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 accentuate the importance of peroxynitrite-driven pathways realized in macrophages via the engagement of NADPH oxidase- and NO synthase-triggered oxidative mechanisms. We consider 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. We evaluate the importance of genetic factors and their manipulations for the enzymatic biodegradation in vivo. Finally, we emphasize a novel type of biodegradation realized via the activation of the "dormant" peroxidase activity of hemoproteins by the nano-surface. This is exemplified by the binding of GO to cyt c causing the unfolding and 'unmasking' of the peroxidase activity of the latter. We conclude with the strategies leading to safe by design carbonaceous nanoparticles with optimized characteristics for mechanism-based targeted delivery and regulatable life-span of drugs in circulation.
• Subjects:
  Animals Humans Nanoparticles Nanotubes, Carbon Neutrophils Oxidation-Reduction Oxidative Stress Peroxidases
• Keywords:
  Carbon Nanotubes Free Radicals Graphene Oxide Oxidants Peroxidase Activity Phagocytes
• Source:
  Toxicol Appl Pharmacol. 299:58-69
• Pubmed ID:
  26768553
• Pubmed Central ID:
  PMC4811710
• Document Type:
  Journal Article
• Funding:
  R01 CA165065/CA/NCI NIH HHSUnited States/ ; R01 OH008282/OH/NIOSH CDC HHSUnited States/ ; R01 NS076511/NS/NINDS NIH HHSUnited States/ ; ES020693/ES/NIEHS NIH HHSUnited States/ ; R01ES019304/ES/NIEHS NIH HHSUnited States/ ; NS076511/NS/NINDS NIH HHSUnited States/ ; CA165065/CA/NCI NIH HHSUnited States/ ; P01 HL114453/HL/NHLBI NIH HHSUnited States/ ; R01 ES019304/ES/NIEHS NIH HHSUnited States/ ; R01 HL086884/HL/NHLBI NIH HHSUnited States/ ; NS061817/NS/NINDS NIH HHSUnited States/ ; R01 ES020693/ES/NIEHS NIH HHSUnited States/ ; U19 AI068021/AI/NIAID NIH HHSUnited States/ ; P01 HL070807/HL/NHLBI NIH HHSUnited States/ ; HL086884/HL/NHLBI NIH HHSUnited States/ ; P30 CA047904/CA/NCI NIH HHSUnited States/ ; P30CA047904/CA/NCI NIH HHSUnited States/ ; R37 NS061817/NS/NINDS NIH HHSUnited States/ ; OH008282/OH/NIOSH CDC HHSUnited States/ ; R01 NS061817/NS/NINDS NIH HHSUnited States/
• Volume:
  299
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:24ee42dcef7d8e6bdb2b0ff07cb5def9349aaef775260aafa02ccfb6571c88bd
• Download URL:
  https://stacks.cdc.gov/view/cdc/38747/cdc_38747_DS1.pdf
• File Type:
  [PDF - 2.36 MB ]