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Enzymatic Oxidative Biodegradation of Nanoparticles: Mechanisms, Significance and Applications
  • Published Date:
    Jan 06 2016
  • Source:
    Toxicol Appl Pharmacol. 299:58-69.


Public Access Version Available on: May 15, 2017 information icon
Please check back on the date listed above.
Details:
  • Pubmed ID:
    26768553
  • Pubmed Central ID:
    PMC4811710
  • Funding:
    CA165065/CA/NCI NIH HHS/United States
    ES020693/ES/NIEHS NIH HHS/United States
    HL086884/HL/NHLBI NIH HHS/United States
    NS061817/NS/NINDS NIH HHS/United States
    NS076511/NS/NINDS NIH HHS/United States
    OH008282/OH/NIOSH CDC HHS/United States
    P01 HL070807/HL/NHLBI NIH HHS/United States
    P01 HL114453/HL/NHLBI NIH HHS/United States
    P01 HL114453/HL/NHLBI NIH HHS/United States
    P30CA047904/CA/NCI NIH HHS/United States
    R01 ES019304/ES/NIEHS NIH HHS/United States
    R01 NS076511/NS/NINDS NIH HHS/United States
    R01 OH008282/OH/NIOSH CDC HHS/United States
    R01ES019304/ES/NIEHS NIH HHS/United States
    U19AIO68021/PHS HHS/United States
  • Document Type:
  • Collection(s):
  • 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.

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