Role of surface chemistry in the toxicological properties of manufactured nanoparticles.
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-009141, 2010 Nov; :1-12
Globally, both industrial workers and the general public are being exposed to a variety of damaging respirable environmental contaminants on a daily basis. Poor air quality has been linked to chronic respiratory diseases and instances of these diseases are increasing worldwide. The last decade has seen the birth of nanotechnology in which the novel properties of engineered nanoparticles are being exploited for advancements in technology and medicine. The driving force for making nanoparticles is to obtain materials with novel electrical, mechanical, optical properties. Knowledge of the reactivity of the surface sites will provide new strategies for reducing risks of occupational hazards. The focus of this project was to study the correlation between the surface reactivity of nanoparticles and their toxicity. The experimental approach focused on several classes of extensively used nanoparticles, with biological endpoints involving oxidative stress and inflammatory responses of aluminosilicate catalysts, titania, quantum dots, silver and carbon. Titania and aluminoslilcates were found to be non-inflammatory. For carbon, the inflammatory response seems to track the size of the particle. Macrophages exposed to synthesized particulates impregnated with iron resulted in secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-a) along with an increase in endothelial cell adhesion molecule expression. In addition, surface iron speciation and content were a driving factor of oxidative stress induced macrophage activation. Quantum dots (QDs) are semiconductor nanocrystals that have found use in bioimaging, cell tracking and drug delivery among other applications. Research regarding the toxicity and fate of QDs in biological systems is relevant to better understand cell/nanoparticle interactions. We have developed an inexpensive, time efficient microwave based synthetic protocol to develop high quality QDs. The biological characterization of these QDs was used to better understand the endocytosis of inorganic nanoparticles by macrophages and associated cellular responses. The QDs associate with scavenger receptors and also are internalized via clathrin dependent endocytosis. Using real-time, live cell imaging, we found that QDs interact with the cell surface within minutes and progress through the endocytic pathway to the lysosomes upon internalization. As demonstrated by assays of LDH release, dead red staining and annexin V staining, we found these QDs to be minimally toxic to exposed macrophages. In addition, QDs induced small but significant levels of TNF-a secretion. Using dye-entrapped aluminosilciate zeolites, we have developed an intracellular oxygen sensor. Human monocyte-derived macrophages internalized the submicron-sized Ru(bpy)32+-zeolite crystals, and intracellular oxygen concentrations initiated by zymosan-mediated oxidative burst could be monitored by measuring the emission from Ru(bpy)32+ by confocal fluorescence microscopy. The antimicrobial properties of patterned aluminosilicate zeolite films containing nanosilver were successfully demonstrated using E-coli bacteria as the model system and complete bacteria eradication was noted within 120 minutes.
Environmental-contamination; Exposure-levels; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system; Pulmonary-system-disorders; Nanotechnology; Surface-properties; Toxic-materials; Toxic-effects; Toxins; Biological-effects; Oxidation; Silver-compounds; Carbonates; Carbonyls; Particulates; Particle-aerodynamics; Cellular-function; Cell-function; Cell-cultures; Stress; Bacteria
Prabir K. Dutta, The Ohio State University, Department of Chemistry, 120 West 18th Avenue, Columbus, Ohio 43210
Final Grant Report
NTIS Accession No.
National Institute for Occupational Safety and Health
Ohio State University