Author Archives: gpyrgiot

Carcinogenic and Fibrogenic Potential of Carbon Nanotubes

Screen Shot 2013-10-18 at 12.56.55 PMDr. Yon Rojanasakul

Professor, 

School of Pharmacy, West Virginia University

 Dr. Liying Wang, M.D.

Adjunct Professor, 

Department of Basic Pharmaceutical Sciences, West Virginia University


Date:         December 12, 2013

Time:          12:30-1:30pm

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.

Challenges in Exposure Assessment: From Nanoparticles to Bioaerosols, by Dr. Gediminas “Gedi” Mainelis

Title: Challenges in Exposure Assessment: From Nanoparticles to Bioaerosols

Speaker: Dr. Gediminas “Gedi” Mainelis 

Associate Professor

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.

Joel Cohen Defended his Doctoral Thesis

Joel

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.

New Publication by Georgios Pyrgiotakis

TOC artwork

Georgios Pyrgiotakis et al. published one of the first attempts to quantify the effect of the protein corona in the nano-bio interactions. The work was carried out in collaboration with the Particle Technology Laboratory at the Swiss Federal Institute of Technology (ETH). Here is the abstract of the publication and the link to access it at Langmuir.

Abstract

Particle–particle interactions in physiological media are important determinants for nanoparticle fate and transport. Herein, such interactions are assessed by a novel atomic force microscopy (AFM)-based platform. Industry-relevant CeO2, Fe2O3, and SiO2nanoparticles of various diameters were made by the flame spray pyrolysis (FSP)-based Harvard Versatile Engineering Nanomaterials Generation System (Harvard VENGES). The nanoparticles were fully characterized structurally and morphologically, and their properties in water and biological media were also assessed. The nanoparticles were attached on AFM tips and deposited on Si substrates to measure particle–particle interactions. The corresponding force was measured in air, water, and biological media that are widely used in toxicological studies. The presented AFM-based approach can be used to assess the agglomeration potential of nanoparticles in physiological fluids. The agglomeration potential of CeO2 nanoparticles in water and RPMI 1640 (Roswell Park Memorial Institute formulation 1640) was inversely proportional to their primary particle (PP) diameter, but for Fe2O3nanoparticles, that potential is independent of PP diameter in these media. Moreover, in RPMI+10% Fetal Bovine Serum (FBS), the corona thickness and dispersibility of the CeO2 are independent of PP diameter, while for Fe2O3, the corona thickness and dispersibility were inversely proportional to PP diameter. The present method can be combined with dynamic light scattering (DLS), proteomics, and computer simulations to understand the nanobio interactions, with emphasis on the agglomeration potential of nanoparticles and their transport in physiological media.

Nano-scale Hyperspectral Microscopy

Title: Nano-scale Hyperspectral Microscopy

Speaker: Byron J. Cheatham, Senior VP, CytoViva, Inc.

Date: Monday July 22

Time: 10:00 am

Place: Room 1302

Abstract: CytoViva, Inc. provides a patented (US patents No. 7,542,203, 7,564,623) nanoscale optical microscope capability integrated with proprietary hyperspectral imaging. This integrated technology was specifically designed for optical observation, spectral characterization and mapping of nano-materials as they interact with biologicals and composite materials. The patented illumination optics of the microscope system utilizes structured oblique-angle illumination to produce a very high signal-to-noise image. Scatter from nano-scale materials imaged with CytoViva’s structured oblique-angle illumination optics can produce as much as seven times more signal intensity when compared to standard darkfield microscope optics.

Integrated hyperspectral imaging on the microscope enables capture of the unique VNIR reflectance spectra (400nm-1,000nm) of nano-scale materials within a wide range of biological and composite environments at a spectral resolution of 2.5nm. The system creates a hyperspectral image of these samples, enabling the nano-materials to be spectrally characterized and mapped throughout the entire sample.

Today over 250 nano-focused laboratories utilize CytoViva technology for nano-drug delivery, nano-toxicology and nano-materials related research initiatives. Additionally the technology is utilized in certain pathogen related studies.

More Info

NIOSH Sub-acute Inhalation Studies with Multi-walled Carbon Nanotubes (MWCNTs) by Vincent Castranova

Castranova

Title: NIOSH Sub-acute Inhalation Studies with Multi-walled Carbon Nanotubes (MWCNTs)

Speaker: Dr. Vincent Castranova 

Chief, Pathology and Physiology Research Branch, NIOSH, 

CDC Distinguished Consultant, 

Professor, Basic Pharmaceutical Sciences, West Virginia University

Professor, Environmental and Occupational Health, University of Pittsburgh


Date: June 24, 2013
Time: 1:30-2:30pm
Place: 665 Huntington Ave, Building 1, Room 1302, Boston, MA 02115

Abstract:Mice were exposed by inhalation to 5 mg/m3 of MWCNT, 5 hours/day, for up to 15 days. Pulmonary responses, MWCNT translocation from the lung, and lung tumor formation were monitored up to 17 months post-exposure. Initial lung burden was approximately 30 ug/lung. MWCNT, deposited in the conducting airways, were cleared within days. However, MWCNT in the respiratory zone exhibited very slow clearance with a half time in the range of 500 days. Inhalation of MWCNT resulted in a rapid inflammatory response which slowly returned toward control over 168 days post-exposure. In addition, collagen within alveolar walls increased with time post-exposure, progressing to a persistent level significantly above control from 84-168 days post-exposure. At 1 days post-exposure, single MWCNT fibers were found in the tracheobronchial lymphatics, the chest wall, diaphragm, and systemic organs. This translocation continued slowly, increasing the number of extra-pulmonary fibers over the 332 day post-exposure period. Tumor formation was evaluated 17 months after inhalation of MWCNT, using an initiation/promotion model. Although MWCNT alone did not induce significant tumors, inhalation of MWCNT substantially increased tumor formation, size, and carcinogenicity after administration of a DNA damaging chemical, methylcholanthrene, indicating that MWCNT act as a potent promoter.  These results will be discussed in relation to the recent NIOSH REL for carbon nanotubes.

Just Announced: CytoViva Visit

The NanoCenter is very happy to host Cytoviva as they present their latest microscope (Cytoviva) that uses the so-called “hyperspectral imaging”, i.e. measuring the scattering profile of samples, and being able to distinguish cells, and different types of materials. Especially for studies of inorganic particles with cells, it offers several advantages because it is a “label-free” detection method. It is not limited to inorganic particles, however, they claim that also lysosomes and other organic particles can be easily detected. It also has the possibility to use standard fluorescent dyes if we install the appropriate filters.

Title: Nano-scale Hyperspectral Microscopy

Speaker: Byron J. Cheatham, Senior VP, CytoViva, Inc.

Date: Monday July 22

Time: 10:00 am

Place: Room 1302

Abstract: CytoViva, Inc. provides a patented (US patents No. 7,542,203, 7,564,623) nanoscale optical microscope capability integrated with proprietary hyperspectral imaging. This integrated technology was specifically designed for optical observation, spectral characterization and mapping of nano-materials as they interact with biologicals and composite materials. The patented illumination optics of the microscope system utilizes structured oblique-angle illumination to produce a very high signal-to-noise image. Scatter from nano-scale materials imaged with CytoViva’s structured oblique-angle illumination optics can produce as much as seven times more signal intensity when compared to standard darkfield microscope optics.

Integrated hyperspectral imaging on the microscope enables capture of the unique VNIR reflectance spectra (400nm-1,000nm) of nano-scale materials within a wide range of biological and composite environments at a spectral resolution of 2.5nm. The system creates a hyperspectral image of these samples, enabling the nano-materials to be spectrally characterized and mapped throughout the entire sample.

Today over 250 nano-focused laboratories utilize CytoViva technology for nano-drug delivery, nano-toxicology and nano-materials related research initiatives. Additionally the technology is utilized in certain pathogen related studies.

More Info

Joseph D. Brain Fellowship

Joe-Brain-feature

Joseph D. Brain is the Cecil K. and Philip Drinker Professor of Environmental Physiology and former chair of the Department of Environmental Health at the Harvard School of Public Health. Dr. Brain joined the Department in 1962 as a young graduate student researching the body’s response to inhaled gases, particulates, and microbes and has remained at the School since that time—teaching and mentoring countless students, engaging in ground-breaking research, and leading his colleagues with fervor and foresight.

To honor Dr. Brain for his significant contributions to the Department of Environmental Health and the field of environmental physiology, the school is in the process of establishing the Joseph D. Brain Fellowship Fund in Environmental Health. The Fund will provide much-needed resources for environmental health scholars to pursue doctoral and post-doctoral study at the Harvard School of Public Health. Support provided by the fund will enable talented and dedicated students who otherwise would be unable to afford tuition and expenses to pursue their educational goals. It also allows the work started by Dr. Brain to be carried out and expanded by promising scholars who are preparing to begin their careers in the field.

New Website!

ne

Our new website is launching soon. A portal to all things nano. Explore the projects, the researcher and the contact the investigators  via the highly interactive website. Use the website to explore our labs and learn more about the upcoming events. Launching day July 1st.

Applications and Environmental Health and Safety Implications of Engineered Nanomaterials and Nanotechnology

Title: Applications and Environmental Health and Safety Implications of Engineered Nanomaterials and Nanotechnology
Date: September 24, 2012
Place: Kyoto University

Abstract: Numerous reports and commissions have documented the explosion of discoveries in nanotechnology. Moreover, these discoveries are quickly moving out of the laboratory into commercial products. It is imperative that the fields of exposure assessment, nanotoxicology and risk assessment be developed in parallel with nanotechnology and its applications. This symposium aims to bring together all stakeholders, industry, academia and regulators and foster productive conversations about this emerging and critical aspect of engineering, commerce, and public health.

Program

12:30‐12:45pm – Welcoming Remarks, Prof. Minoru Yoneda, Kyoto University 12:45‐

12:50pm – Greetings from Harvard University Session 1: Chaired by Dr. Philip Demokritou

12:50‐1:00pm – Welcoming remarks by Prof. Philip Demokritou, Harvard School of Public Health (HSPH)

1:00‐1:30pm – ““Environmental Health Implications of Engineered Nanomaterials and Nanotechnology: What we know and what we do not know”, Prof. Philip Demokritou, HSPH

1:30‐2:00pm –“Green Nanotechnology: Aiding Sustainability”, Dr. Barbara Karn, National Science Foundation, USA

2:00‐2:30pm – ʺRisk Assessment as a requirement for nanomaterial innovation: Regulatory status and voluntary approaches”, Dr Atsuo Kishimoto, National Institute of Advanced Industrial Science and Technology, Japan

2:30‐3:00pm – “Exposure Assessment of Market Products including nanomaterials in general use and their disposal”, Dr Yasuto Matsui, Kyoto University.

3:00‐3:30pm – Questions/Discussion

3:30‐3:50pm – Coffee Break

3:50‐5:15pm –“Engineered water nanostructures: synthesis, physico‐chemical properties and pathogen disinfection applications”, Dr. Georgios Pyrgiotakis, HSPH

5:15‐5:40pm – “Biological and toxicological properties of inhaled engineered water nanostructures”, Prof. Joseph Brain, HSPH

5:40‐6:05pm –“Nanoparticle behavior in the developing lungs”, Dr Akira Tsuda, HSPH

6:05‐6:30pm –“Formation and transport mechanisms of highly charged nanodroplets”, Dr Yoshio Otani, Kanazawa University, Japan

6:30‐6:55pm – “Biological safety evaluation of electrostatic atomized water using tests for genotoxicity and reproductive toxicity”, Ryo Ota and Yuzuki Nakagawa, Hatano Research Institute, Japan.

6:55‐7:20pm – “Performance evaluation of a novel ionizer for air purification applications”, Dr Stephen Rudnick, HSPH

7:20‐7:30pm – Closing Remarks, Prof. Minoru Yoneda, Kyoto University Session 2: Chaired by Dr. Joseph Brain 7:30‐8:30pm – Reception