Grantee Research Project Results
2006 Progress Report: Iron Oxide Nanoparticle-Induced Oxidative Stress and Inflammation
EPA Grant Number: R831722Title: Iron Oxide Nanoparticle-Induced Oxidative Stress and Inflammation
Investigators: Elder, Alison C.P. , Oberdörster, Günter , Yang, Hong , Finkelstein, Jack
Institution: University of Rochester
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2004 through February 28, 2008
Project Period Covered by this Report: September 1, 2005 through February 28, 2006
Project Amount: $335,000
RFA: Exploratory Research to Anticipate Future Environmental Issues: Impacts of Manufactured Nanomaterials on Human Health and the Environment (2003) RFA Text | Recipients Lists
Research Category: Nanotechnology , Safer Chemicals , Human Health
Objective:
The manufacture of nanoparticles (NPs; < 100 nm diameter) of varying shapes and compositions has exploded over the last several years, with applications ranging from diagnostic imaging to nanoscale molecular construction, thus making intentional and unintentional human exposures likely. Although much has recently been learned about their synthesis, the study of nanomaterials effects in cells and tissues is in its infancy. As has also been hypothesized for nanosized ambient air, or ultrafine particles, engineered NPs may evade clearance mechanisms at the site of deposition, thus potentially coming into contact with epithelial and endothelial cells and translocating to sites distant from the original exposure. It is also possible that inflammation and oxidant stress will occur as a result of unique NP properties, including their large surface area and reactivity, or from prolonged retention. We are addressing these hypotheses with the following objectives to determine if NPs: (1) induce oxidative stress and toxicity in cultured epithelial and endothelial cells; (2) cause lung inflammation or extrapulmonary effects after in vivo exposure; and (3) are translocated to extrapulmonary sites.
Progress Summary:
:The first year of the project was focused on creating NP systems that could be used to test our hypotheses and assessing their stability in various exposure media. Much of the second year of this project was spent in a thorough analysis of the effects (e.g., cytotoxicity, evidence of oxidative stress) of Pt nanoparticle shapes (e.g., flowers, multipods, flower spheres, and pod spheres; 11-35 nm; 1-27 m2/g) and their uptake by endothelial cells. All Pt shapes have the same composition. In an acellular assay of reactive oxygen species generating capacity (oxidation of fluorescent probe), the Pt flowers and flower spheres had the highest activity, likely due to their higher surface area, as compared to the other two shapes. The overall activity of all Pt shapes is low, similar to that of nanosized TiO2 and Ag. An analysis of the responses of epithelial and endothelial cells to these particles over a wide range of doses (0.01-500 μg/well; 0.003-132 μg/m2) and times (0-48 hours) showed that the Pt shapes induce oxidative stress only at the highest doses. The effects of the nanoshapes in endothelial cells on lactate dehydrogenase and interleukin-6 release are similar to those caused by nanosized TiO2. It is possible that NP agglomeration/aggregation in culture medium could mask the effects of smaller singlets. To the extent that agglomeration is partly dependent on concentration, our exposures at the lowest dose (0.01 μg/well) suggest that large and small aggregates have similar effects for the same material. Electron microscopic (EM) evaluation of the NP suspension (25 μg/mL) revealed a mixture of singlets and aggregates/agglomerates. Another open question was whether or not endothelial cells would take up the Pt shapes. EM analyses of fixed, exposed cells revealed intracellular accumulations of aggregated Pt flowers and multipods at two different dose levels (25 and 500 μg/mL). We analyzed cell pellet and culture supernatant samples via inductively coupled plasma mass spectrometry in order to quantitate the uptake of Pt flowers and multipods at four dose levels. We found that Pt flowers were taken up at twice the rate of the multipods and that more Pt was found in the cells than in the supernate at the lower doses. In vivo studies conducted in rats exposed to quantum dots (QDs) via the respiratory tract or intravenous injection showed that surface coating determines tissue retention, that QDs delivered to the lungs are transported to extrapulmonary tissues, and that injected QDs accumulate in the lungs (although it is not yet known if they are stuck in the vasculature or in the alveolar spaces). These studies with what appear to be low-toxicity particles, through comparison with other metal NPs, are helping to define the cellular uptake of nanomaterials and the dependency of physicochemical characteristics on uptake and effects.
Future Activities:
We will focus our efforts over the next several months on in vivo analyses of metal and metal oxide NP effects and tissue distribution. The specific activities that are planned for the immediate future include the following: (1) continue work to characterize the physicochemical characteristics of the particles used for exposures; (2) evaluate uptake and distribution of NPs, both qualitatively and quantitatively following in vivo exposure; and (3) evaluate lung inflammation and oxidative stress after exposure.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
Other project views: | All 9 publications | 4 publications in selected types | All 4 journal articles |
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Maksimuk S, Teng X, Yang H. Planar tripods of platinum: formation and self-assembly. Physical Chemistry Chemical Physics 2006;8(40):4660-4663. |
R831722 (2006) |
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Teng XW, Liang XY, Maksimuk S, Yang H. Synthesis of porous platinum nanoparticles. Small 2006;2(2):249-253. |
R831722 (2006) |
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Supplemental Keywords:
nanoparticles, oxidative stress, inflammation, endothelial cells, epithelial cells, nanoparticle uptake, nanoparticle tissue distribution,, Health, Scientific Discipline, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Risk Assessments, Physical Processes, Biology, Risk Assessment, lung injury, lung epithelial cells, toxicology, exposure, nanotechnology, human exposure, lung inflamation, iron oxide nanoparticles, cellular response to nanoparticles, exposure assessment, human health riskProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.