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NIEHS Launches NanoHealth Signature Program

By Eddy Ball
August 2010

Stavros Garantziotis, M.D.
Like many scientists, Garantziotis is intrigued by the applications of nanotechnology, but concerned about how much is still unknown about ENMs. "The problem," he said, "is that we just don't know what the health effects may be.... A dose which may be innocuous for a healthy person may have adverse effects in a susceptible person, such as an asthmatic." (Photo courtesy of Steve McCaw)

Six months ago a team of investigators led by NIEHS Clinical Research Unit Medical Director and Matrix Biology Group Head Stavros Garantziotis, M.D., began preliminary studies for a novel, interdisciplinary and interagency project now underway to investigate the health effects of widely used engineered nanomaterials (ENM) in susceptible populations.

ENMs are increasingly found in medications, cosmetics, electronics, and other consumer products, creating environmental as well as occupational exposures. The study is one of several launched in the past year in response to the NIH Nanoscience and Nanotechnology in Biology and Medicine Program ( Exit NIEHS.

Public health potential

According to Garantziotis, the research will have important public health implications. "The unique physicochemical characteristics of nanomaterials enable new applications," he wrote in a summary of the project, "but may also engender new health risks, particularly in vulnerable populations, such as individuals with pre-existing lung disease." Understanding more about modes of action, he added, could also lead to improved efforts to better design safety into the ENMs to which humans are most commonly exposed.

The physical, chemical, and biological properties of ENMs, which range in size from roughly 1 to 100 nanometers, differ from the properties of individual atoms and molecules, or of bulk matter. According to the NIH booklet "Nanotechnology at the National Institutes of Health," nanoscale devices smaller than 50 nanometers can easily enter most cells, while those smaller than 20 nanometers can move out of blood vessels as they circulate through the body - raising concerns among many environmental health scientists about their potentially harmful health effects.

A three-phase approach

Over the next three years, Garantziotis and colleagues in the Clinical Research Unit (CRU) will engage in bidirectional collaborations with the National Toxicology Program (NTP), labs in the NIEHS intramural program, and the U.S. Environmental Protection Agency (EPA) as they explore the effects of exposure among healthy and susceptible populations to ENMs that are already present in the atmosphere, as part of the Intramural NanoHealth Signature Program. The team will study the effects in cells tissue, animals, and human subjects.

According to Garantziotis, the research team will test the hypothesis that selected engineered nanomaterials induce pulmonary inflammation and that asthmatic individuals are particularly susceptible to engineered nanomaterial effects, in a translational exposure model with three aims:

  • Exposing human bronchial epithelia and alveolar macrophages - native lungs cells donated by healthy volunteers - to ENMs ex vivo to evaluate inflammation and cell toxicity
  • Comparing the ex vivo response to ENMs of human bronchial epithelia and alveolar macrophages between healthy and asthmatic individuals to understand whether pre-existing disease alters the effect of ENMs on human cells
  • Performing controlled chamber exposures of human volunteers to select ENMs of interest to assess the potential for effects on lung function and inflammation

A three-pronged collaboration across divisions and agencies

This novel collaboration will pilot nanomaterial research in the NIEHS intramural program among clinical and basic researchers and introduce translational research collaboration among the NTP Nanotechnology Safety Initiative, the NIEHS extramural program and its grantees working on ENMs, and the U.S. Environmental Protection Agency (EPA), where bronchoscopy and controlled exposures of human subjects will take place.

Garantziotis said he expects information transfer to be robust and bidirectional. "We will compare our findings to animal toxicology findings from NTP and EPA," Garantziotis added, "to establish the relevance of the animal models." Animal studies may also suggest ENMs for further human testing, and investigators in the extramural consortium will likewise benefit from, and contribute to, ongoing clinical research.

A Precedent-Setting Network of Collaboration

The Nanohealth and Safety Initiative includes five components - materials science research, basic biology, pathobiology research, informatics, and training - that draw upon the talents of scientists from throughout NIEHS and its grantee community. In his presentation to NIEHS/NTP Director Linda Birnbaum, Ph.D., Garantziotis offered special thanks to 12 of his colleagues:

  • Andrew Ghio, M.D., pulmonologist and clinical researcher at the EPA, who is collaborating in the human study component of the project
  • Erika Gutierrez, predoctoral fellow in the NIEHS Clinical Research Program, who is performing ex vivo experiments on human cells using ENMs
  • Ron Herbert, D.V.M., Ph.D., leader of the NTP Pathology Support Group who is assisting in the analysis of results
  • Ivy Ji, Ph.D., scientist at the University of California, Los Angeles (UCLA) and the California NanoSystems Institute
  • Pat Mastin, Ph.D., acting deputy director of the Division of Extramural Research and Training
  • Sri Nadadur, Ph.D., DERT health scientist administrator overseeing the nanotechnology grants portfolio
  • Andre Nel, M.D., professor of Medicine, Pediatrics and Public Health at UCLA, chief of the UCLA Division of NanoMedicine, and NIEHS grantee researching ENMs
  • Annette Rice, a biologist working in the NIEHS Clinical Research Program who is performing ex vivo experiments on human cells using ENMs
  • Sally Tinkle, Ph.D., NIEHS senior science advisor and lead in interagency and trans-NIH working groups on NanoHealth issues
  • Nigel Walker, Ph.D., NTP deputy program director for science and lead for the NTP Nanotechnology Safety Initiative
  • Darryl Zeldin, M.D., acting director of the NIEHS Clinical Research Program
  • Jeffrey Zink, Ph.D., distinguished professor of chemistry at UCLA

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