Cross-sectional autoradiograms of rodent brains showing (A) control physiological state; and (B) and (C) showing
distribution of brain injury from an injected neurotoxicant. Red areas indicate the highest concentrations of a
biomarker that identifies brain areas that are damaged by the neurotoxicant. Credit: Guilarte Lab
Little is known about how engineered nanomaterials and nanoparticles impact human health and the environment. Particles at the scale of one-billionth of a meter—so small they can slip across the blood-brain barrier—pose many questions about the safety of nanotechnology used in products consumed and used by humans. The Institute for NanoBioTechnology at Johns Hopkins University recently awarded $100,000 to fund research projects that seek to answer these questions. Four $25,000 seed grants were given to multidisciplinary research teams to fund pilot projects across Johns Hopkins.
Risk assessment performed in tandem with research into beneficial applications will help researchers make better decisions about how nanotechnology is used in the future, says Jon Links, professor at the Bloomberg School of Public Health and INBT’s director of Health and Environment research. “The history of technological research and development is full of examples of unrecognized risks to health and the environment—chlorofluorocarbons or asbestos are examples,“ Links says. “It is imperative to study potential risks to human health and the environment hand-in-hand with benefit-driven research and development. Doing so provides the best chance to minimize risk, because risk assessment can inform research and development at an early stage, leading to alternative pathways.“
Nanoparticles made of silica, for example, can be used to deliver pharmaceuticals. But despite the potential benefits, scientists don’t have much information on what happens to these particles after they have offloaded their cargo. Principal investigators from the Bloomberg School of Public Health (BSPH) and the Whiting School of Engineering (WSE) plan to use a protein to measure the toxicity of silica nanoparticles in the brain cells of rodents.
“There is a tremendous interest in using nanomaterials in various aspects of medicine, including delivery of drugs to the brain,“ says Tomas Guilarte, professor of environmental health sciences in the BSPH and a co-investigator on this study. “However, the possibility that the nanomaterial itself produces brain injury has not been evaluated.“
In another proposed study, collaborators from the BSPH and WSE will measure how the shape, size, and function of engineered silica-silicone hybrid nanomaterials affect cellular uptake and response using advanced methods for cell imaging and biomarker assessment. This research also will address questions relating to dose and exposure.
The Katz Lab is looking at ways to bind fluorescent dyes to nanoparticles for use in tumor tissue imaging. Shown are nanoparticles containing 1048 dye after deposition for scanning electron microscopy. Credit: Katz Group / JHU
“Once these particles reach cells, it is important to know whether they penetrate into cells, whether cells survive this penetration, and whether the biochemistry inside these cells is altered,“ says Howard Katz, professor of materials science and engineering. “These methods will permit us to visualize where nanomaterials are located in cells, and the nature of any response by these cells,“ adds Ellen Silbergeld, professor of Environmental Health Sciences.
Multi-walled carbon nanotubes are commonly used engineered nanoparticles that have been exploited for their exceptional strength, as well as their chemical, optical and electrical properties. But these particles also are known to bind toxic heavy metals. If the nanotubes wind up in the food chain, they could deposit toxic metals in the stomachs of animals or humans. The fate of these metals will be examined in an in vitro study developed by researchers from the Krieger School of Arts and Sciences, (KSAS), WSE and BSPH.
“Given their extremely high surface area to mass ratios, small amounts of carbon nanotubes have the potential to transport relatively large amounts of adsorbed toxins,“ says William Ball, professor of Geography and Environmental Engineering. “In this way, the carbon nanotubes could effectively act as ‘Trojan horses’ that may bring toxic contaminants to locations that they may not otherwise reach.“
Nanoparticles made of silver oxide, silver nitrate, silver chloride and titanium dioxide can be found in many household products–from the coatings on washing machines to personal care products. These particles may enter the ecosystem through waste water and affect aquatic life. Investigators from public health, arts and sciences, and engineering will track those particles to see if any show up in oysters commercially harvested from the Chesapeake Bay.
“In the water, engineered nanoparticles can alter oyster immune defense mechanisms, making them more susceptible to oyster diseases,“ says Thaddeus Graczyk, associate professor in the Bloomberg School of Public Health. “As oysters are predominantly consumed raw, nanoparticles recovered from the water by oysters and retained in their tissue will enter the human food chain.“
These pilot projects represent some of the ongoing research at INBT, which seeks to balance benefit-driven applications of nanotechnology with risk assessment. Finding from these investigations will no doubt have policy implications for the use of nanoparticles. “Since inaccurately perceived risks by the public and legislators can slow development and adoption of beneficial technologies, accurate assessment and timely dissemination of the actual risks is becoming more and more critical,“ Links says. “Relatively little is known about the potential ecologic and human toxicity of nanomaterials, so INBT’s pilot project program is critical.“
Below is a complete list of pilot program titles and the names of the members of each research team involved:
- “Neurotoxicological and intracellular effects of NPs,“ Tomas Guilarte, (Professor, Environmental Health Sciences, BSPH) and Howard Katz (Professor, Materials Science and Engineering, WSE).
- “Quantifying the interactions between lymphocytes and engineering nanomaterials: effects of surface modification on cell uptake, distribution and response,“ Howard Katz (Professor, Materials Science and Engineering, WSE), Ellen Silbergeld (Professor, Environmental Health Sciences, BSPH), and Jennifer Nyland (Research Associate, BSPH).
- “Intestinal desorption and transport properties of metals adsorbed onto carbon nanotubes,“ Joseph Bressler (Associate Professor, Environmental Health Sciences, BSPH and Kennedy Krieger Institute); Howard Fairbrother (Professor, Chemistry, KSAS); and William Ball (Professor, Geography and Environmental Engineering, WSE).
- “Nanoparticle transport and fate in the aquatic environment; filter-feeding oysters as a target organism,“ Thaddeus Graczyk (Associate Professor, Environmental Health Sciences, BSPH), Ken Livi (Microbeam Lab Coordinator, KSAS), Kai Loon Chen (Assistant Professor, Geography and Environmental Engineering, WSE); K.T. Ramesh (Professor, Mechanical Engineering, WSE) and Denis Wirtz (Professor, Chemical and Biomolecular Engineering, WSE).
INBT GRANT PROPOSAL SERVICE
INBT offers help to Johns Hopkins University faculty that wish to submit a nanobiotechnology related grant proposal. Seed grants awarded by INBT must have more than one principal investigator. Principal investigators must be from different schools or departments. To learn more about INBT’s grant proposal service, please contact Sue Porterfield at firstname.lastname@example.org or call 410-516-3423.
Story by Mary Spiro