Enzymatic oxidative biodegradation of nanoparticles: Mechanisms, significance and applications
Journal Article
·
· Toxicology and Applied Pharmacology
- Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219 (United States)
- Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 (United States)
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261 (United States)
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. - Highlights: • Nanoparticles can be degraded by oxidative enzymatic machinery of inflammatory cells. • Peroxidase-generated oxidants are the reactive species executing the biodegradation. • Unmasked by GO binding peroxidase activity of cyt c biodegrades GO. • Professional phagocytes are accountable for the clearance of nanoparticles in vivo. • Carbonaceous nano-carriers of drugs protect against degradation of payloads.
- OSTI ID:
- 22689166
- Journal Information:
- Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 299; ISSN TXAPA9; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Aptamer/Graphene Oxide Nanocomplex for In Situ Molecular Probing in Living Cells
Structure-activity relationships in the free-radical metabolism of xenobiotics
Efficient internalization of silica-coated iron oxide nanoparticles of different sizes by primary human macrophages and dendritic cells
Journal Article
·
Mon Jun 21 00:00:00 EDT 2010
· Journal of the American Chemical Society, 132(27):9274–9276
·
OSTI ID:988651
Structure-activity relationships in the free-radical metabolism of xenobiotics
Journal Article
·
Sun Sep 01 00:00:00 EDT 1985
· Environ. Health Perspect.; (United States)
·
OSTI ID:5718574
Efficient internalization of silica-coated iron oxide nanoparticles of different sizes by primary human macrophages and dendritic cells
Journal Article
·
Wed Jun 01 00:00:00 EDT 2011
· Toxicology and Applied Pharmacology
·
OSTI ID:21535306