New England Nanotechnology Association

News | Center for Nanotechnology and Nanotoxicology

jcbonnerTitle: Predicting the Impact of Engineered Nanomaterials on Lung Diseases

Speaker: Dr. James C. Bonner

Associate Professor

Department of Environmental & Molecular Toxicology,

North Carolina State University, Raleigh, NC

665 Huntington Ave, Building 1, Room 1302, Boston, MA 02115

Abstract: The nanotechnology revolution offers enormous societal and economic benefits for innovation in the fields of engineering, electronics, and medicine. Nevertheless, evidence from rodent inhalation studies show that biopersistent engineered nanomaterials, including carbon nanotubes and metal nanoparticles, have the potential to stimulate immune, inflammatory, or fibroproliferative responses in the lung and pleura. These data suggest possible risks for pulmonary fibrosis or the development of pleural disease as a consequence of occupational or consumer exposure. Some engineered nanomaterials also exacerbate pre-existing allergen-induced inflammation by altering the balance of distinct T-helper cell phenotypes, suggesting that they could serve as sensitizers or adjuvants to alter the innate immune response. These findings suggest that individuals with asthma or other pre-existing respiratory diseases would be particularly susceptible to the adverse health effects of nanomaterials. Due to their nanoscale dimensions and increased surface area per unit mass, engineered nanomaterials have a much greater potential to reach the distal regions of the lung, generate reactive oxygen species, and alter cell signaling pathways linked to disease pathogenesis. The goal of this presentation will be to discuss mechanisms through which engineered nanomaterials cause lung, airway, and pleural disease, especially in the context of susceptible individuals with pre-existing disease. Functionalization of nanomaterials through processes such as atomic layer deposition will also be discussed as a means of altering the pathogenicity of nanomaterials.

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Nanomaterials are part of daily life. Although there is a wide range of methods to evaluate their potential toxic effects, there is no way to evaluate gene damage.

Scientists at Harvard University in the School of Public Health in collaboration with the research Group of Bevin P. Engelward at MIT, have developed a screening assay to detect the genotoxic potential of nanomaterials. Metal oxide nanoparticles in biological systems can generate reactive oxygen species, which can overwhelm innate antioxidant defenses and cause oxidative stress. Oxidative stress, among other factors, has been associated with DNA damage and mutations, precursors to cancer. As more and more commercial products contain nanomaterials consisting of metal oxides such as titanium dioxide and zinc oxide, screening assays such as these are crucial to reducing potential health hazards. Christa Watson, postdoctoral research fellow at HSPH, suggests that accurate toxicity assessments of nanomaterials before they are incorporated into consumer products can help us prevent similar consequences that we are currently facing from asbestos exposures such as mesothelioma. Current efforts are ongoing to understand the novel toxicities nanomaterials may pose on public safety. This research was recently published in ACS Nano February 14, 2014 DOI: 10.1021/nn404871p

Protocol for the high throughput Comet Assay. (A) Assembly of macrowell comet array. Agarose gel with microwells is sandwiched between a glass substrate and a bottomless 96-well plate and sealed with mechanical force. Approximately 300 arrayed microwells comprise the bottom of each macrowell. (B) Preparation of the nanoparticle suspension according to the protocol by Cohen at al. (C) Protocol for exposing the cells to the nanoparticles. (D) Loading of the exposed cell samples in the macrowells and running the microwell assay. photo Screen Shot 2014-01-27 at 5.00.42 PM
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