Title: Predicting the Impact of Engineered Nanomaterials on Lung Diseases
Speaker: Dr. James C. Bonner
Department of Environmental & Molecular Toxicology,
North Carolina State University, Raleigh, NC
Date: February 27, 2014
Time: 12:30-1:30 pm
Place: 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.
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.
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
ZnO is a widely used material in cosmetics and food applications. The ions however, that are leaching have been linked to potential adverse effects. In our center we developed a safer formulation concept to mitigate toxicity by encapsulating the materials in a thin layer of Silica.
One of the main constituents of sunscreen is the ZnO particles. ZnO nanoparticles are sought out for UV-filter applications thanks to their inherent optoelectronic properties and are, therefore, broadly used today in cosmetics and polymers. Preliminary toxicological data, however, point out that they can induce significant DNA damage and genotoxicity due to their Zn2+ ion leaching. It has become important for the nanotechnology industry, to devise scalable, safer-by-design approaches to minimize the ZnO nanoparticle dissolution and toxicity without altering their desired optoelectronic properties.
G. Sotiriou the lead author of the paper.
In their work, the researchers demonstrated a safer-by-design approach for ZnO nanorods using a scalable flame aerosol process. This technology allows for controlled synthesis of high-purity ZnO nanorods with highly crystalline core and a nanothin amorphous silica shell that improves their biocompatibility. The as-prepared nanorods exhibit high transparency in the visible range, but strong absorption in the UV rendering them suitable for use in sunscreens and polymers. Furthermore, it is demonstrated that the hermetic silica coating does not alter the desired optoelectronic properties of the core ZnO nanorods while their DNA damage potential has been 3-fold decreased.
You can read more at the Chemistry World news article or, directly the paper.
Please join us for our next meeting of the Massachusetts chapter of the New England Nanotechnology Association (NENA) to hear about some new developments in nanotechnology and nanotoxicology.
We’ll enjoy a continental breakfast, spend a little time networking, and hear about these new developments and other topics of interest. There is no cost to attend, so please RSVP today. Thank you and we look forward to seeing you soon.
8:30 – 9:00AM: Networking and refreshments
9:00 – 9:10AM: Welcome and introductions - William S. Rogers, Jr., Esq., Partner, Prince Lobel Tye LLP, Boston, MA
9:10-9:20AM: Speaker - Eric S. Howard, Corporate and Outreach Manager, NSF Center for High-rate Nanomanufacturing, Northeastern University, Boston, MA
9:20-9:35AM: Speaker - Philip Demokritou, Ph. D., Assoc. Professor and Director, Center for Nanotechnology and Nanotoxicology, Harvard School of Public Health, Cambridge, MA
9:35-9:45AM: Speaker - Joseph Brain, Ph.D., Cecil K. and Philip Drinker Professor of Environmental Physiology, Department of Environmental Health, Harvard School of Public Health, Cambridge, MA
9:45-10:00: Networking and adjourn
Click here to RSVP – deadline is 2/21/14
Can’t make the event? Join our LinkedIn Discussion Page.
We must have a complete list of attendees two days prior to the event in order to arrange visitor passes. No one can get in without a visitor’s pass.
If you have any questions, please don’t hesitate to contact me.
William S. Rogers, Jr.
Prince Lobel Tye LLP
During their visit a delegation from Panasonic headed by Mr. Oketa continued their financial support to the Center of Nanotechnology and Nanotoxicology through a generous contribution to the Environmental Nanotechnology postdoctoral Fellowship.
The panasonic delegates that visited our center were Takemi Oketa, Mitsuhiro Sano and Yosuke Mizuyama.
In the image above Prof. Demokritou receives the gift from Mr. Oketa in front of Dr. Mizuyama, Pyrgiotakis and Mr. Sano.
Phil Demokritou et al. published recently a high impact paper at the Enviromental Science: Nano a new Journal from the Royal Society of Chemistry. Environmental Science: Nano covers the benefits and implications of nano-science and nanotechnology on environmental health and safety, and the sustainable design, development and use of nanotechnologies. This includes design, applications, life cycle implications, characterization in biological and environmental media, environmental and biological interactions and fate, transformations, transport, reactivity, biological uptake and ecotoxicity, and other areas of sustainable nanotechnology, such as interactions with pollutants and remediation of environmental contaminants by nanomaterials.
Our publication fits the objective of the journal and it was selected by the editors as the most innovative research article to decorate the cover of the first issue of the journal. You can find here the abstract of the paper and the link to the publisher. If you have access to the RSC you will be able to access the publications.
Abstract: Airborne pathogens are associated with the spread of infectious diseases and increased morbidity and mortality. Herein we present an emerging chemical free, nanotechnology-based method for airborne pathogen inactivation. This technique is based on transforming atmospheric water vapor into Engineered Water Nano-Structures (EWNS) via electrospray. The generated EWNS possess a unique set of physical, chemical, morphological and biological properties. Their average size is 25 nm and they contain reactive oxygen species (ROS) such as hydroxyl and superoxide radicals. In addition, EWNS are highly electrically charged (10 electrons per particle on average). A link between their electric charge and the reduction of their evaporation rate was illustrated resulting in an extended lifetime (over an hour) at room conditions. Furthermore, it was clearly demonstrated that the EWNS have the ability to interact with and inactivate airborne bacteria. Finally, inhaled EWNS were found to have minimal toxicological effects, as illustrated in an acute in-vivo inhalation study using a mouse model. In conclusion, this novel, chemical free, nanotechnology-based method has the potential to be used in the battle against airborne infectious diseases.
Dr. Jacqueline Isaacs
Department of Mechanical and Industrial Engineering Northeastern University, Boston, MA
Date: January 23, 2014
Place: 665 Huntington Ave,
Bldg 1, Room 1302,
Boston, MA 02115
Abstract: Responsible commercialization of nano-enabled products (NEPs) will encompass not only the successful development of economically viable manufacturing techniques, but also, a conscious and systematic consideration of short and long-term societal impacts to avoid unintended consequences. The US National Nanotechnology Initiative has urged for more effective use of life cycle analysis (LCA) in decision-making, which in turn demands greater consideration of the ethical, legal, and social impacts (ELSI) of nanomanufacturing as it scales to commercial production. As part of its mission to establish novel directed self-assembly processes and techniques for continuous and scalable nanomanufacturing, the NSF Nanoscale Science and Engineering Center for High-rate Nanomanufacturing (CHN at Northeastern University, the University of Massachusetts Lowell and the University of New Hampshire) is developing three CNT applications that will soon move to large-scale production: electromagnetic interference (EMI) shielding, batteries, and chemical- and bio- sensors. Our current research (involving researchers from NU, UML and Yale) leverages CHN’s technical efforts by developing knowledge about life cycle impacts of CNT-enabled products – from manufacturing, through use and end-of-life. Worker safety is considered during manufacture and at product disposal in light of the uncertain hazards of CNTs. Process economics that include various levels of protection are explored. Recycled nanomaterials are explored for technical viability. Exposure assessments during end-of-life processing offer options to avoid exposures. Policy issues for responsible, sustainable development of nano-enabled products are also concurrently assessed.
Dr. Yon Rojanasakul
School of Pharmacy, West Virginia University
Dr. Liying Wang, M.D.
Department of Basic Pharmaceutical Sciences, West Virginia University
Date: December 12, 2013
Place: 665 Huntington Ave,
Bldg 1, Room 1302,
Boston, MA 02115
Abstract: Carbon nanotubes (CNTs) are high-aspect ratio nanomaterials that have increasingly been used in a wide variety of commercial applications owing to their unique properties such as high tensile strength, extreme light weight, and high electrical and thermal conductivity. There is a great concern about the potential pathogenicity of CNTs because of their biopersistence, mode of exposure, and structure similarity to asbestos fiber, which is a known human pathogen causing mesothelioma and asbestosis. Our laboratories have been investigating the long-term health effects of CNT exposure with a focus on lung carcinogenesis and fibrosis. There is evidence that CNTs can gain access to the nucleus and cause genetic aberrations. A recent animal exposure study indicates the tumor promoting effect of CNTs. Studies in our laboratories have shown that chronic exposure of human lung epithelial cells to CNTs induces malignant transformation of the cells as demonstrated by anchorage-independent cell growth, loss of contact inhibition, increased cell invasion, and acquired apoptosis resistance. The transformed cells also induce tumorigenesis in mice, supporting the potential tumorigenicity of CNTs in humans. CNTs also induce pulmonary fibrosis, a pathology that is often associated with particle-induced lung cancer. This talk will focus on the in vitro and in vivo evidence of lung pathologies caused by CNTs and will examine the potential underlying mechanisms with the goal of developing mechanism-based risk assessment and early detection strategies.
Title: Challenges in Exposure Assessment: From Nanoparticles to Bioaerosols
Speaker: Dr. Gediminas “Gedi” Mainelis
Department of Environmental Sciences, Rutgers University,
The State University of New Jersey, NJ, USA
Date: October 17, 2013
Time: 12:30 pm – 1:30 pm
Place: 665 Huntington Ave, Building 1, Room 1302, Boston, MA 02115
Abstract: Health-relevant aerosols present a challenging and multi-faceted aerosol research area ranging from nanoparticles, to environmental exposures to indoor aerosols. Mainelis’ lab at Rutgers University has been actively investigating potential exposures to engineered nanoparticles from consumer products and developing novel tools for bioaerosol exposure assessment. We recently began investigation of potential consumer exposures to nanoparticles due to the use of nanotechnology-based consumer products. To realistically simulate potential exposures, we used a manikin head with simulated inhalation through its nostrils, while the products were used nearby (sprays) or applied to the manikin’ face (cosmetic powders). We found that the tested nanotechnology-based products released particles not only in the nanosize range but also in coarse and for some products in super-coarse particle size ranges. The release and inhalation of nanoparticles and their agglomerates in such a wide size range would result in particle deposition in all regions of the respiratory system and thus, health studies should focus not only on single nanoparticles, but also on deposition and health effects of larger agglomerates. To improve bioaerosol exposure assessment, we have been developing a novel electrostatic collector for bioaerosols, where biological particles are electrostatically deposited onto a narrow electrode covered by a superhydrophobic substance and then removed and collected by a rolling water droplet (5 to 40 microliters) to achieve an unprecedented sample concentration rate, whichrate allows detecting lower bioaerosol concentrations. It is hoped that this technique will improve our ability to assess exposures to bioaerosols in various air environments.
On September 23, Joel Cohen defended his doctoral thesis on Nanotoxicology. Joel over the course of his studies published several peer reviewed papers, one book chapter and awarded one patent (with his coworkers).
Join us in congratulating Joel Cohen for successfully defending his ScD thesis and obtaining his doctoral degree!
Thesis Abstract: There is a great need for screening tools capable of rapidly and accurately assessing engineered nanomaterial (ENM) toxicity. One impediment to the development of reliable in vitro screening methods is the need for accurate and relevant dosimetry. In a typical in vitro cytotoxicity study ENM powders are suspended in liquid media for application to cells. ENMs in liquid suspension can form large fractal agglomerates thereby altering (1) the total number of free particles, (2) the total surface area available for biointeractions, and (3) the effective size and density of the particles, two properties that influence their fate and transport and determine the effective dose actually delivered to cells in culture over the duration of exposure. I present here a methodology for in vitro nanotoxicology that takes into consideration particokinetics and enables accurate determination and reporting of effective dosimetry. This methodology is based upon (1) standardization of ENM liquid suspension preparation; (2) careful characterization of critical ENM transformations in exposure media including agglomerate effective density; and (3) numeric calculation of the delivered to cell dose as a function of exposure time.
This methodology is then employed to investigate ENM translocation across cellular monolayers in vitro. Relatively little is known about the fate of industrially relevant engineered nanomaterials (ENMs) in the lungs. These interactions are important when considering inhalation exposure and subsequent translocation of ENMs across the thin epithelial lining layer of the lung. I present a novel method for tracking well-characterized industrially relevant metal oxide ENMs made radioactive in vitro. Nano-sized CeO2 of various primary particle diameter (27 and 119nm), ZnO, SiO2-coated-CeO2 and SiO2-coated-ZnO particles generated by flame spray pyrolysis were neutron activated in a nuclear reactor, forming the gamma emitting isotopes 141Ce and 65Zn respectively. To investigate ENM translocation using an in vitro model for the alveolar epithelium, we cultured Calu-3 lung epithelial cells cultured to confluency on transwell inserts with 3μm pores and exposed them to neutron activated ENM dispersions below the pre-determined toxic dose. The effects of ENM exposure on monolayer barrier integrity and tight junctions were evaluated, and ENM translocation across the cellular monolayer was assessed following 2, 4 and 24 hours of exposure by gamma spectrometry. My results demonstrate that industrially relevant ENM agglomerates translocate predominantly via a transcellular pathway without compromising monolayer integrity or disrupting tight junctions. In order from greatest to least translocation the ENMs investigated rank as follows: ZnO> SiO2 coated ZnO > SiO2 coated CeO2 > CeO2 large > CeO2 small. I also demonstrate the effects of particle transport translocation across the alveolar epithelium, emphasizing the importance of accurate dosimetry when comparing ENM-cellular interactions for large panels of materials.