Nanotechnology has enormous potential for biomedical applications and is being investigated for diagnostics (e.g., imaging, sensors) and therapeutics (e.g., implants, devices, drug delivery). However, a major challenge must first be met: to understand and quantify the relationship between nanoparticle characteristics and physiological responses. How nanoparticles composition, shape, charge, surface chemistry, and particle size relate to the integration of a material into a living organism, especially to sensitive cell system-stem cells, is largely unknown. Stem cells are a unique cell population with the ability to undergo both self-renewal and differentiation. Adult stem cells constantly provide new cell lineages in our body. Recently increasing amount of evidence suggest that stem cells may be the sources of mutant cells that give rise to cancerous tumors and maintain tumor growth. Our previous studies indicated the carbon nanotube and nanosilver particles can induce a DNA damage response in mouse embryonic stem cells. In this proposal, four types of nanoparticles (carbon, silver, titanium dioxide, and zinc oxide) will be manufactured and the toxicity to stem cells will be assessed. The study will help us better understand the impact of nanoparticles to stem cell fate and develop the methods to evaluate the health and safety of nanoparticles and greatly enhance consumer confidence. In addition, this research will enhance the research for graduate and undergraduate students at the University of Dayton.

Public Health Relevance

The nanotechnology revolution has the potential to top the industrial revolution and turn over $1 trillion. There is a need to determine the toxicity of manufactured nanoparticles and their impact on human health and the environment, especially to stem cells. Stem cells have the ability to divide indefinitely, and can give rise to many different cell lineages. The functions and properties of stem cells are very different from that of somatic cells. Mutation in stem cells can give rise to cancer and potentially compromise multiple cells lineages and affect the well being of subsequent generations. The objective of this project is to understand the impact of the nanoparticles to stem cell fate and to develop a rapid and cost effective protocol for determination of the toxicity of manufactured nanoparticles to stem cells. This proposal will provide a comprehensive database of toxicity of manufactured nanoparticles to stem cells and greatly enhance consumer confidence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15ES019298-01A1
Application #
8102275
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Nadadur, Srikanth
Project Start
2011-09-01
Project End
2012-08-01
Budget Start
2011-09-01
Budget End
2012-08-01
Support Year
1
Fiscal Year
2011
Total Cost
$129,605
Indirect Cost
Name
University of Dayton
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
073134025
City
Dayton
State
OH
Country
United States
Zip Code
45469
Repar, Neza; Li, Hao; Aguilar, Jose S et al. (2018) Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived neuron and astrocyte network. Nanotoxicology 12:104-116
Begum, Aynun N; Aguilar, Jose S; Hong, Yiling (2017) Aqueous cigarette tar extracts disrupt corticogenesis from human embryonic stem cells in vitro. Environ Res 158:194-202
Begum, Aynun N; Aguilar, Jose S; Elias, Lourdes et al. (2016) Silver nanoparticles exhibit coating and dose-dependent neurotoxicity in glutamatergic neurons derived from human embryonic stem cells. Neurotoxicology 57:45-53
Begum, Aynun N; Guoynes, Caleigh; Cho, Jane et al. (2015) Rapid generation of sub-type, region-specific neurons and neural networks from human pluripotent stem cell-derived neurospheres. Stem Cell Res 15:731-741
Rajanahalli, Pavan; Stucke, Christopher J; Hong, Yiling (2015) The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation. Toxicol Rep 2:758-764