The Wise Laboratory of Environmental and Genetic Toxicology

Nanotoxicology Studies

Human Toxicology

Nanotoxicology Studies

Background | References | Collaborators | Funding

Nano 1

 

Background

Nanotechnology is considered to be the next industrial revolution and likely to become a $1 trillion dollar industry within the next 10 years (1).The federal government is already investing $1 billion in nanotechnology development. Nanoparticles are currently in use in commercial products including sunscreen, stain-resistant clothing, semiconductors, tires, and sports equipment like bowling balls (1). One of the major potential applications for nanoparticles is their use as drug delivery systems. They are already being tested in clinical trials for drug delivery in diseases such as pancreatic cancer and the National Institutes of Health announced 4 nanomedicine development centers this past fall. We are in the beginning of the coming age of nanotechnology.

Nano

Nanoparticles are defined as having at least one dimension with a size less than 100 nm. They exist in the quantum scale, which means that they don't follow the known laws of solids, liquids or gases (1). Instead, their properties are defined by quantum mechanics, which gives them their value. Potential applications may include: Printable inks for flexible electronics, biomedical assays, drug delivery, sunscreen and cosmetics, textile, colorants and paints, solar cells, liquid crystal displays, and chemical catalysis, to name a few (2-8). They exhibit mechanical, magnetic, electronic, and color properties unachievable by these same chemicals at larger size scales. For example, large, bulky metallic gold particles were considered to be almost completely inert, and as such have historically not been investigated for commercial uses as a chemical reactant. However, gold nanoparticles can behave as strong catalysts for a broad range of commercially and industrially viable chemistries (8-9). Consequently, a whole new industry is emerging with vastly significant new products and markets.

However, the same properties that make these particles exciting in technology and consumer markets also make them daunting public health concerns. Simply put, whether or how these new properties will enhance, diminish or otherwise alter the toxicity of the compounds from which they are derived is not known. The toxicity of nanoparticles is unknown and relatively unexplored. This lack of data is remarkable given the use of the technology in high consumer-use products like clothes and sunscreen.

Engineered nanoparticles clearly exhibit toxic effects in rodent studies that have shown that inhaled nanoparticles accumulate in the nasal passage, lung, and brain (10) where they can cause lesions that interfere with oxygen absorption (11) and cause suffocation caused by immune system cells clumping around the particles and blocking bronchial passages (12). However, these studies were conducted at very high exposure levels and the real toxic potential at lower levels is uncertain. Recently, it has been shown that lower doses also cause respiratory toxicity including proinflammatory and fibrotic responses (13). Cell culture studies confirm the toxicity of engineered nanoparticles and report cytotoxicity, decreased cell viability, and the production of proinflammatory agents (14-16). These cell culture studies indicate that size and particle composition can dramatically modify toxicity, with some sizes and forms highly toxic and others nontoxic (16-17).

Our work is focused on determining the effects of nanoparticles on DNA and genomic stability, and thus their potential carcinogenicity.

We are using human lung cells, to determine the cellular and molecular effects of metal nanoparticles including gold, silver, and copper. We are considering the possible effects of size, agglomerate properties, composition, shape and surface composition, and determining how these parameters affect the ability of metal nanoparticles to damage DNA (measured as strand breaks and chromosome damage) and induce genomic instability.

 

References

  1. Hood, E. Nanotechnology: Diving into the unknown. Environmental Health Perspective. 112: A747-A749, 2001.

  2. Fuller, S.B., Wilhelm, E.J., Jacobson, J.M. Ink-Jet Printed nanoparticle microelectromechanical systems. Journal of Microelectromechanic System 11:54-60, 2002.

  3. Maxwell, D.J., Taylor, J.R., and Nie, S. Self-assembled nanoparticle probes for recognition and detection of biomolecules. Journal of the American Chemical Society 124: 9606-9612, 2002.

  4. Salata, O. Applications of nanoparticles in biology and medicine. Journal of Nanobiotechnology 2: 3-8, 2004.

  5. Bishop, P.T. The use of gold mercaptides for decorative precious metal applications. Gold Bulletin 35: 89-98, 2002.

  6. Law, M., Greene, L.E., Johnson, J.C., Saykally, R., and Yang, P. Nanowire dye-sensitized solar cells. Nature Letters 4: 455-459, 2005.

  7. Shiraishi, Y., Maeda, K., Yoshikawa, H., Xu, J., Toshima, N., and Kobayashi, S. (2002) Frequency modulation response of a liquid-crystal electro-optic device doped with nanoparticles. Applied Physics Letters 81: 2845-2847, 2002.

  8. Haruta, M. Gold Rush. Nature 437: 1098-1099, 2005.

  9. Hughes, M.D., Xu, Y.J., Jenkins, P., McMorn, P., Landon, P., Enache, D.I., Carley, A.F., Attard, G.A., Huthcings, G.J., King, F., Stitt, E.H., Johnston, P., Griffin, K., and Kiely, C.J. Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions. Nature Letters 437: 1132-1135, 2005.

  10. Oberdorster, G., Sharp, Z., Atudorei, V., Elder, A., Gelein, R., Kreyling, W., and Cox, C. Translocation of inhaled ultrafine particles to the brain. Inhalation Toxicology 16:437-45, 2004.

  11. Lam, C.W., James, J.T., McCluskey, R., and Hunter, R.L. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicological Science 77:126–134, 2004.

  12. Warheit, D.B., Laurence, B.R., Reed, K.L., Roach, D.H., Reynolds, G.A.M., and Webb, T.R. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicological Science 77:117–125, 2004.

  13. Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J.F., Delos, M., Arras, M., Fonseca, A., Nagy, J.B., and Lison, D. Respiratory toxicity of multi-wall carbon nanotubes. Toxicology and Applied Pharmacology 207: 221-31, 2005.

  14. Monteiro-Riviere, N.A., Nemanich, R.J., Inman, A.O., Wang, Y.Y., Riviere, and J.E. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicology Letters 155:377-84, 2005.

  15. Shvedova, A.A., Castranova, V., Kisin, E.R., Schwegler-Berry, D., Murray, A.R., Gandelsman, V.Z., Maynard, A., and Baron, P. Exposure to carbon nanotube material: assessment of nanotube cytotoxicity using human keratinocyte cells. Journal of Toxicology and Environmental Health Part A 66:1909-26, 2003.

  16. Sayes, C. M., Fortner, J. D., Guo, W., Lyon, D., Boyd, A. M., Ausman, K. D., Tao, Y. J., Sitharaman, B., Wilson, L. J., Hughes, J. B., West, J. L., and Colvin, V. L. The differential cytotoxicity of water-soluble fullerenes. Nano Letters 4: 1881-1887, 2004.

  17. Goodman, C.M., McCusker, C.D., Yilmaz, T., and Rotello, V.M. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains Bioconjugate Chemistry 15: 897-900, 2004.

     

Collaborators and Cooperators

The Wise Laboratory is assisted in this work by a number of important collaborators and cooperators. In particular, the following prominent scientists and their teams provide significant support and input:

Dr. Michael Masonis an Assistant Professor in the Department of Chemical and Biological Engineering at the University of Maine and a member of the Institute for Molecular Biophysics. He provides expertise in nanoparticle properties particularly single molecule and quantum dot chemistry and photophysics as well as in the design and application of new ultra-sensitive chemical imaging techniques, including both fluorescence and Raman spectroscopies.

Dr. Ah-Kau Ngis Professor of Immunology in the Department of Applied Medical Sciences at the University of Southern Maine. He and Dr. Wise are collaborating on a project considering the immunotoxicological effects of nanoparticles.

Dr. Gunter Oberdorsteris Professor of Environmental Medicine at the University of Rochester College of Medicine. He provides expert advice and guidance in nanotoxicology.

Dr. Lisa Pfefferleis Professor of Mechanical Engineering and the Chair of the Department of Chemical Engineering at Yale University. She provides expert advice and guidance on the creation and characterization of dusts and particles.

Dr. Douglas Thompson>is a Professor of Epidemiology and Associate Director of the Maine Center for Toxicology and Environmental Health at the University of Southern Maine. He provides expert advice and guidance on statistical analysis and study design.

 

Funding

This work is generously supported by the Maine Center for Toxicology and Environmental Health.