Scientists continually push the frontiers of science into uncharted territory. Some defy our imagination. And many come at a cost.
Nanomaterials have been at the forefront of scientific research for more than a decade. These tiny materials are defined as microscopic substances measuring 1 nm to 100 nm in size. Nanoparticles are up to one million times thinner than a human hair.
Because of its small size, nanoparticles have large surface area-to-volume ratios. These materials offer a range of properties that can be different from larger configurations of the same substance – typically enhanced strength, chemical reactivity, or electrical conductivity. And those properties can be leveraged in many ways. Manufactured nanoparticles may find practical applications in a variety of areas, including medicine, engineering, catalysis, manufacturing and environmental remediation.
Christie Sayes, Ph.D., Associate Professor, Baylor University
Many held a common belief that nanoparticles may have a higher risk of toxicity compared to larger particles, due to its higher chemical reactivity and biological activity. These nanoscopic particles can enter the body through inhalation, ingestion and dermal penetration because of the small size of these substances. Once inside the body, nanoparticles are able to pass through cell membranes and may interact with sub-cellular components.
Nanotoxicity, or nanotoxicology refers to the potential adverse health effects related to engineered nanomaterial exposure, according to Christie Sayes, Ph.D. Sayes is an Associate Professor in the Department of Environmental Science at Baylor University. Her research delves into the effects of these nanomaterials on living tissues and whole animal systems.
Animal studies in the past decade have shown that some nanoparticles can penetrate into cells and through tissues. These may move through the body, reach vital organs like the heart or the brain, cause biochemical damage, and may contribute to the progression of disease.
You cross paths with nanoparticles every day. Nanoparticle applications range from strengthening fibers in cloths to increasing power in computer hard drives. Nanotechnology also plays an important role in the manufacture of numerous consumer products that we use regularly.
The benefits can be found in electronics and information technology applications, medical and healthcare applications, energy storage and distribution, and contaminant remediation in the environment.
Scientists and engineers have had great success developing materials at the nanoscale to take advantage of its enhanced properties of higher strength, lighter weight, increased electrical conductivity, and bioactivity, compared to its larger-scale equivalents. Engineered nanoparticles are used in hundreds of ways.
Transistors, the basic switches that enable all modern computing, have become smaller through nanotechnology processes. The materials can be incorporated into solar panels to convert sunlight to electricity more efficiently, promising inexpensive solar power in the future.
An optical hyperspectral image overlaid on an enhanced darkfield image. Red highlights carbon nanotube (agglomerated), purple highlights lung tissue, and blue highlight lung cell nuclei.
Engineered nanoparticles can be more toxic than larger particles because they can move more freely than bulkier molecules. The body’s natural defenses against foreign invaders were generally designed for larger particles.
Exposure to nanoparticles had been previously associated with a range of acute and chronic effects. These range from inflammation, exacerbation of asthma, and metal fume fever to fibrosis, chronic inflammatory lung diseases, and carcinogenesis, as reported by the National Institutes of Health. Various studies have demonstrated that inhaled or ingested nanoparticles could enter systemic circulation and migrate to different organs and tissues.
A confocal laser scanning micrograph of human gastro-intestinal cells in culture. Green highlight cell surface membrane, Blue highlights cell nuclei, and Red highlight mitochondria.
Toxicities that happen at the cellular level are unique, according to Sayes. If a cell understands that it's going through a substantial amount of damage, it has this control mechanism called apoptosis, which simply means cellular suicide. The cell might recognize it’s undergoing some toxic event and may choose to eliminate itself before that toxicity might spread to other surrounding cells into organs, organ systems, or the entire body. It’s a defense mechanism that animals and plants have against a contamination. So what happens at the cellular level sometimes may not extrapolate out to the entire organism level.
“It's important to know the route of exposure and the concentration of what you might have been exposed to, and then you can characterize the effects,” she said.
Gold nanoparticles that are less than 20 nm in diameter.
Sayes said most of the time when a toxicologist, or an environmental health specialist talks about nanotoxicology or nanotoxicity, they are referring to adverse health effects that happens at the cellular level. That’s because a nanomaterial is so small, that the very first interaction that a nanomaterial might have after exposure occurs at the cellular level.
“It’s an interface between the inorganic, synthetic engineered nanomaterial with the organic cell membrane,” she said. “At that interface there could be some chemical or biochemical reactions that occur. That is something nanotoxicologists can observe, measure, and characterize.”
Nanoparticles have been shown time and time again to penetrate and permeate through cell membranes, but it’s also able, because of its small size, to travel in our airways, in the lungs to areas that larger particles usually cannot reach. In fact, some studies have shown that nanoparticles can translocate from the lung to the circulatory system.
Yet, the individual threat that nanomaterials might pose hasn’t been borne out.
“There've been many hypotheses over the last 15 years that perhaps exposure to engineered nanomaterials may pose a different kind of threat than other types of substances,” she said. “But the literature hasn't really revealed threats that are unique to nanomaterials.”
Not that nanomaterials don’t pose a danger that’s worth studying.
“We have seen increased vulnerabilities in different organ systems,” Sayes said. “For instance, nanoparticles, when they are aerosolized and you breathe them in, they're able to reach the distal areas of the lung, where larger-sized particles are not able to deposit or reach. But the extent of the toxicity or the dose needed to elicit an adverse response is a lot lower when you're exposed to a nanomaterial as opposed to a bulk size or micro-sized particle.”
The threshold or the concentration of a nanoparticle inducing a response is lower than what a concentration of that same material might be. So it takes less nanoparticles to elicit the same response that a larger particle might elicit.
“Occupational workers are the cohort of individuals that would be exposed to the higher level of detrimental effects, because they would be exposed to aerosolized nanopowders that exist before it's formulated into a slurry, to go into a product,” Sayes said.
That would include those working in a manufacturing facility that uses nanomaterials as part of its production process.
But down the line, ordinary people are exposed to nanoparticles that inevitably become mixed with other materials, which make these particles grow in size. Nanoparticles change rapidly as it gets more mature in the product development pipeline.
“By the time a consumer might be exposed to a product that had nanoparticles in it, the likelihood of them being exposed to a pristine particle is very small,” Sayes said. “In fact, they would be exposed to a formulation that may contain a small concentration of nanoparticles inside.”
It may have lost its nano properties, or the nano properties may have been diminished.
Nanomaterials may enter the ecosystem through many routes. One is through wastewater treatment facilities, via a washing machine’s discharge, where nanomaterials enhance the detergents for your laundry. Agriculturally, growers might use nano-enabled fertilizer, pesticide or herbicide. Those would be applied to crops or to animals and food. Runoff from the crops or from the animal itself can penetrate into soil or into water as well.
“Nanoparticles or nanomaterials do not easily degrade,” Sayes said. “That's part of the reason why nanochemists and material scientists like them so much, because they're very stable. So they tend to be persistent in the environment, meaning they stay intact in soil and water and air for a long time. It of course depends on the size and the charge and the composition for exactly how long that is, but you can detect particles. We have detected particles in air, water, soil and in human tissues.”
Yet nanomaterials are fundamentally no different than any other type of material particle or chemical in terms of toxicity.
There are various properties, features or descriptors about individual nanomaterials that make them more or less toxic. One is the chemical composition. The chemical composition becomes one of the main predictors of what the potential adverse health outcome would be if you were exposed to it. Therefore, its toxicity is no different than nanomaterials depending on its composition on the atomic scale. It also includes the particular elements and structure that are present. That could be a predetermination of what the toxicity might be.
For instance, a nanomaterial that contains a heavy metal such as cadmium or lead, might be more cytotoxic, or toxic to living cells, than a nanomaterial that contains something more inert like carbon or oxygen or silicon.
“I think people should be worried about toxicities, period,” Sayes said. “So, in the same way that you should be worried about chemical exposures or environmental exposures or pharmaceutical exposures, you should also be worried about exposures to engineered nanomaterials. At the end of the day, exposure and hazard are related to the dose or the concentration of the material and with the substance in which you're exposed to.”
Sayes believes people should be worried about toxicity or toxicities in general, be it exposures to pharmaceuticals, chemicals, environmental agents, or engineered nanomaterials. An engineered nanomaterials is just one of many things that we should be aware of.
“I'm concerned about the mixtures of things I'm exposed to,” she said. “I'm not so worried about the nanomaterials that might be in my sunscreen that I apply to my face in the summertime, but maybe it's the co-exposure of the sunscreen plus breathing in some poor air quality or maybe water drinking water that had contamination. It's the combination of multiple exposures and the persistent exposures and accumulation of multiple materials that really is understudied. And that's probably where the biggest uncertainty is.”
Not that science hasn’t made progress.
“The toxicology community has a pretty good idea of what the toxicities are for exposure to individual materials, but we do not have as good of an understanding if we're exposed to multiple nanoparticles simultaneously, or a nanomaterial plus some other type of contaminants,” she said.
If nanomaterials don’t pose any considerable health concerns on its own, then why all the hype in the popular press?
“I think there was lots of uncertainty in the scientific community,” Sayes said. “It might be outdated perceptions, because that particular perception was accurate five, 10, 15 years ago. We are beginning to design experiments to answer these hazard questions. Perhaps there has been a lag of the public’s understanding of nano hazards behind that of the scientists. It could be that the science is a little bit further along as opposed to the general population’s understanding or education on the topic. Perhaps there needs to be more of a concerted effort to communicate what we have found in the literature to the general public.”
HORIBA XploRA™ Plus Confocal Raman Microscope coupled with the CytoViva Enhanced Darkfield and Hyperspectral Imaging system
The research into nanotoxicity continues. Sayes studies interactions of nanomaterials and organic tissue at the cellular level. She uses a HORIBA XploRA™ Plus Confocal Raman Microscope coupled with the CytoViva Enhanced Darkfield and Hyperspectral Imaging system. It’s a highly specialized instrument produced through a collaboration between HORIBA Scientific and CytoViva. The device combines Raman microscopy with optical hyperspectral imaging, according to HORIBA AFM-Raman Applications Scientist Maruda Shanmugasundaram, Ph.D.
“The two technologies, based on how each of them work are similar to each other, and can provide very complementary information,” Shanmugasundaram said. “Hence, data obtained with the two technologies from the same sample area can be cross-correlated with one another.”
As a result of the integration, the combined microscope platform provides both wide-field imaging (reflection, transmission, brightfield, darkfield, polarized light and epi-fluorescence) and hyperspectral imaging (Raman, fluorescence, photoluminescence, transmittance and reflectance) modes.
What it does, Sayes said, is allow researchers to study the nanomaterials absorbed by the tissue and the tissue itself in a non-destructive way. It provides not only visual and qualitative information, but it can also quantify the type of reaction that might be happening. In some cases, there are strong biochemical reactions. In other cases, there aren't.
“It's important for us to understand the nature of that interaction, so that we can further understand what type of toxicities might be induced,” she said. “They could be more cytotoxic.”
Her study’s goal was to develop novel metrology (measurement techniques) to be able to gain information about the inorganic nanomaterial, in this case, carbon nanotubes, and the biological system, in this case, mouse lung tissue, on the same platform at the same time, with a method that does not destroy the sample.
Sayes said her research demonstrates a model for future studies.
“My collaboration with HORIBA is an excellent example of researchers in academia collaborating with researchers in industry, to not only prepare samples for a toxicological study, but also to use this unique instrument, an instrument that's specifically designed to gain qualitative and quantitative information on a toxicological tissue sample,” she said. “Raman microscopy can be combined with hyperspectral imaging to provide measurable information on both carbon nanotubes and lung tissue simultaneously.”
It’s a topic of study that adapts well to inter-agency collaboration.
“Nanotoxicology is an area where academics can partner with industry and the government, with researchers and regulators, in developing experimental designs, executing studies and interpreting the results in a highly collaborative, interdisciplinary manner,” Sayes said. “We get multiple perspectives from multiple stakeholders on every aspect of the study, and it makes it lucrative and fun and rewarding.”
Although nanotoxicity research continues, toxicity may be more related to the composition of the material, not the size.
“Nanomaterials are like any other substance, and they could contribute to the onset of many different diseases or conditions,” Sayes said. “It's just that none of them (diseases or conditions) are unique to nanomaterials. There are other materials that can also induce those same effects. But the fact that they're so small, and they may acquire these different chemical properties, does not affect the type of induced toxicity. But it does affect the extent of toxicity.”
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