Tag Archives: Xiang Wang

Faster predictive toxicology of nanomaterials

As more nanotechnology-enabled products make their way to the market and concerns rise regarding safety, scientists work to find better ways of assessing and predicting the safety of these materials, from an Aug. 13, 2016 news item on Nanowerk,

UCLA [University of California at Los Angeles] researchers have designed a laboratory test that uses microchip technology to predict how potentially hazardous nanomaterials could be.

According to UCLA professor Huan Meng, certain engineered nanomaterials, such as non-purified carbon nanotubes that are used to strengthen commercial products, could have the potential to injure the lungs if inhaled during the manufacturing process. The new test he helped develop could be used to analyze the extent of the potential hazard.

An Aug. 12, 2016 UCLA news release, which originated the news item, expands on the theme,

The same test could also be used to identify biological biomarkers that can help scientists and doctors detect cancer and infectious diseases. Currently, scientists identify those biomarkers using other tests; one of the most common is called enzyme-linked immunosorbent assay, or ELISA. But the new platform, which is called semiconductor electronic label-free assay, or SELFA, costs less and is faster and more accurate, according to research published in the journal Scientific Reports.

The study was led by Meng, a UCLA assistant adjunct professor of medicine, and Chi On Chui, a UCLA associate professor of electrical engineering and bioengineering.

ELISA has been used by scientists for decades to analyze biological samples — for example, to detect whether epithelial cells in the lungs that have been exposed to nanomaterials are inflamed. But ELISA must be performed in a laboratory setting by skilled technicians, and a single test can cost roughly $700 and take five to seven days to process.

In contrast, SELFA uses microchip technology to analyze samples. The test can take between 30 minutes and two hours and, according to the UCLA researchers, could cost just a few dollars per sample when high-volume production begins.

The SELFA chip contains a T-shaped nanowire that acts as an integrated sensor and amplifier. To analyze a sample, scientists place it on a sensor on the chip. The vertical part of the T-shaped nanowire converts the current from the molecule being analyzed, and the horizontal portion amplifies that signal to distinguish the molecule from others.

The use of the T-shaped nanowires created in Chui’s lab is a new application of a UCLA patented invention that was developed by Chui and his colleagues. The device is the first time that “lab-on-a-chip” analysis has been tested in a scenario that mimics a real-life situation.

The UCLA scientists exposed cultured lung cells to different nanomaterials and then compared their results using SELFA with results in a database of previous studies that used other testing methods.

“By measuring biomarker concentrations in the cell culture, we showed that SELFA was 100 times more sensitive than ELISA,” Meng said. “This means that not only can SELFA analyze much smaller sample sizes, but also that it can minimize false-positive test results.”

Chui said, “The results are significant because SELFA measurement allows us to predict the inflammatory potential of a range of nanomaterials inside cells and validate the prediction with cellular imaging and experiments in animals’ lungs.”

Here’s a link to and a citation for the paper,

Semiconductor Electronic Label-Free Assay for Predictive Toxicology by Yufei Mao, Kyeong-Sik Shin, Xiang Wang, Zhaoxia Ji, Huan Meng, & Chi On Chui. Scientific Reports 6, Article number: 24982 (2016) doi:10.1038/srep24982 Published online: 27 April 2016

This paper is open access.

Smaller (20nm vs 110nm) silver nanoparticles are more likely to absorbed by fish

An Oct. 8, 2015 news item on Nanowerk offers some context for why researchers at the University of California at Los Angeles (UCLA) are studying silver nanoparticles and their entry into the water system,

More than 2,000 consumer products today contain nanoparticles — particles so small that they are measured in billionths of a meter.

Manufacturers use nanoparticles to help sunscreen work better against the sun’s rays and to make athletic apparel better at wicking moisture away from the body, among many other purposes.

Of those products, 462 — ranging from toothpaste to yoga mats — contain nanoparticles made from silver, which are used for their ability to kill bacteria. But that benefit might be coming at a cost to the environment. In many cases, simply using the products as intended causes silver nanoparticles to wind up in rivers and other bodies of water, where they can be ingested by fish and interact with other marine life.

For scientists, a key question has been to what extent organisms retain those particles and what effects they might have.

I’d like to know where they got those numbers “… 2,000 consumer products …” and “… 462 — ranging from toothpaste to yoga mats — contain nanoparticles made from silver… .”

Getting back to the research, an Oct. 7, 2015 UCLA news release, which originated the news item, describes the work in more detail,

A new study by the University of California Center for Environmental Implications of Nanotechnology has found that smaller silver nanoparticles were more likely to enter fish’s bodies, and that they persisted longer than larger silver nanoparticles or fluid silver nitrate. The study, published online in the journal ACS Nano, was led by UCLA postdoctoral scholars Olivia Osborne and Sijie Lin, and Andre Nel, director of UCLA’s Center for Environmental Implications of Nanotechnology and associate director of the California NanoSystems Institute at UCLA.

Nel said that although it is not yet known whether silver nanoparticles are harmful, the research team wanted to first identify whether they were even being absorbed by fish. CEIN, which is funded by the National Science Foundation, is focused on studying the effects of nanotechnology on the environment.

In the study, researchers placed zebrafish in water that contained fluid silver nitrate and two sizes of silver nanoparticles — some measuring 20 nanometers in diameter and others 110 nanometers. Although the difference in size between these two particles is so minute that it can only be seen using high-powered transmission electron microscopes, the researchers found that the two sizes of particles affected the fish very differently.

The researchers used zebrafish in the study because they have some genetic similarities to humans, their embryos and larvae are transparent (which makes them easier to observe). In addition, they tend to absorb chemicals and other substances from water.

Osborne said the team focused its research on the fish’s gills and intestines because they are the organs most susceptible to silver exposure.

“The gills showed a significantly higher silver content for the 20-nanometer than the 110-nanometer particles, while the values were more similar in the intestines,” she said, adding that both sizes of the silver particles were retained in the intestines even after the fish spent seven days in clean water. “The most interesting revelation was that the difference in size of only 90 nanometers made such a striking difference in the particles’ demeanor in the gills and intestines.”

The experiment was one of the most comprehensive in vivo studies to date on silver nanoparticles, as well as the first to compare silver nanoparticle toxicity by extent of organ penetration and duration with different-sized particles, and the first to demonstrate a mechanism for the differences.

Osborne said the results seem to indicate that smaller particles penetrated deeper into the fishes’ organs and stayed there longer because they dissolve faster than the larger particles and are more readily absorbed by the fish.

Lin said the results indicate that companies using silver nanoparticles have to strike a balance that recognizes their benefits and their potential as a pollutant. Using slightly larger nanoparticles might help make them somewhat safer, for example, but it also might make the products in which they’re used less effective.

He added that data from the study could be translated to understand how other nanoparticles could be used in more environmentally sustainable ways.

Nel said the team’s next step is to determine whether silver particles are potentially harmful. “Our research will continue in earnest to determine what the long-term effects of this exposure can be,” he said.

Here’s an image illustrating the findings,

Courtesy ACS Nano

Courtesy ACS Nano

Here’s a link to and a citation for the paper,

Organ-Specific and Size-Dependent Ag Nanoparticle Toxicity in Gills and Intestines of Adult Zebrafish by Olivia J. Osborne, Sijie Lin, Chong Hyun Chang, Zhaoxia Ji, Xuechen Yu, Xiang Wang, Shuo Lin, Tian Xia, and André E. Nel. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b04583 Publication Date (Web): September 1, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

US multicenter (Nano GO Consortium) study of engineered nanomaterial toxicology

Nano Go Consortium is the name they gave a multicenter toxicology study of engineered nanomaterials which has pioneered a new approach  in the US to toxicology research. From the May 6, 2013 news item on Azonano,

For the first time, researchers from institutions around the country have conducted an identical series of toxicology tests evaluating lung-related health impacts associated with widely used engineered nanomaterials (ENMs).

The study [on rodents] provides comparable health risk data from multiple labs, which should help regulators develop policies to protect workers and consumers who come into contact with ENMs.

The May 6, 2013 North Carolina State University news release, which originated the news item, describes the results from one of two studies that were recently published by the Nano GO Consortium in Environmental Health Perspectives,

The researchers found that carbon nanotubes, which are used in everything from bicycle frames to high performance electronics, produced inflammation and inflammatory lesions in the lower portions of the lung. However, the researchers found that the nanotubes could be made less hazardous if treated to remove excess metal catalysts used in the manufacturing process or modified by adding carboxyl groups to the outer shell of the tubes to make them more easily dispersed in biological fluids.

The researchers also found that titanium dioxide nanoparticles also caused inflammation in the lower regions of the lung. Belt-shaped titanium nanoparticles caused more cellular damage in the lungs, and more pronounced lesions, than spherical nanoparticles.

Here’s a link to and a citation for this study on rodents,

Interlaboratory Evaluation of Rodent Pulmonary Responses to Engineered Nanomaterials: The NIEHS NanoGo Consortium by James C. Bonner, Rona M. Silva, Alexia J. Taylor, Jared M. Brown, Susana C. Hilderbrand, Vincent Castranova, Dale Porter, Alison Elder, Günter Oberdörster, Jack R. Harkema, Lori A. Bramble, Terrance J. Kavanagh, Dianne Botta, Andre Nel, and Kent E. Pinkerton. Environ Health Perspect (): .doi:10.1289/ehp.1205693  Published: May 06, 2013

And the information for the other study which this consortium has published,

Interlaboratory Evaluation of in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS NanoGo Consortium by Tian Xia, Raymond F. Hamilton Jr, James C. Bonner, Edward D. Crandall, Alison Elder, Farnoosh Fazlollahi, Teri A. Girtsman, Kwang Kim, Somenath Mitra, Susana A. Ntim, Galya Orr, Mani Tagmount8, Alexia J. Taylor, Donatello Telesca, Ana Tolic, Christopher D. Vulpe, Andrea J. Walker, Xiang Wang, Frank A. Witzmann, Nianqiang Wu, Yumei Xie, Jeffery I. Zink, Andre Nel, and Andrij Holian. Environ Health Perspect (): .doi:10.1289/ehp.1306561 Published: May 06, 2013

Environmental Health Perspectives is an open access journal and the two studies are being offered as ‘early’ publication efforts and will be updated with the full studies at a later date.

Most interesting for me is the editorial offered by four of the researchers involved in the Nano GO Consortium, from the editorial,

Determining the health effects of ENMs presents some unique challenges. The thousands of ENMs in use today are made from an enormous range of substances, vary considerably in size, and take a diversity of shapes, including spheres, cubes, cones, tubes, and other forms. They are also produced in different laboratories across the world using a variety of methods. In the scientific literature, findings on the properties and toxicity of these materials are mixed and often difficult to compare across studies. To improve the reliability and reproducibility of data in this area, there is a need for uniform research protocols and methods, handling guidelines, procurement systems, and models.

Although there is still much to learn about the toxicity of ENMs, we are fortunate to start with a clean slate: There are as yet no documented incidences of human disease due to ENM exposure (Xia et al. 2009). Because ENMs are manmade rather than natural substances, we have an opportunity to design, manufacture, and use these materials in ways that allow us to reap the maximum benefits—and minimal risk—to humans.

With $13 million from the American Recovery and Reinvestment Act (2009), the National Institute of Environmental Health Sciences (NIEHS) awarded 13 2-year grants to advance research on the health impacts of ENMs (NIEHS 2013). [emphasis mine] Ten grants were awarded through the National Institutes of Health (NIH) Grand Opportunities program and three were funded through the NIH Challenge Grants program. One goal of this investment was to develop reliable, reproducible methods to assess exposure and biological response to nanomaterials.

Within the framework of the consortium, grantees designed and conducted a series of “round-robin” experiments in which similar or identical methods were used to perform in vitro and in vivo tests on the toxicity of selected nanomaterials concurrently at 13 different laboratories.

Conducting experiments in a round-robin format within a consortium structure is an unfamiliar approach for most researchers. Although some researchers acknowledged that working collaboratively with such a large and diverse group at times stretched the limits of their comfort zones, the consortium ultimately proved to be “greater than the sum of its parts,” resulting in reliable, standardized protocols that would have been difficult for researchers to achieve by working independently. Indeed, many participants reflected that participating in the consortium not only benefitted their shared goals but also enhanced their individual research efforts. The round-robin approach and the overall consortium structure may be valuable models for other emerging areas of science.

Here’s a link to and a citation for the Consortium’s editorial, which is available in full,

Nano GO Consortium—A Team Science Approach to Assess Engineered Nanomaterials: Reliable Assays and Methods by Thaddeus T. Schug, Srikanth S. Nadadur, and Anne F. Johnson. Environ Health Perspect 121(2013). http://dx.doi.org/10.1289/ehp.1306866 [online 06 May 2013]

I like the idea of researchers working together across institutional and geographical boundaries as that can be a very powerful approach. I hope that won’t devolve into a form of institutionalized oppression where individual researchers are forced out or ignored. In general, it’s the outlier research that often proves to be truly groundbreaking, which often generates extraordinary and informal (and sometimes formal) resistance. For an example of groundbreaking work that was rejected by other researchers who banded together informally, there’s Dan Shechtman, 2011 Nobel Laureate in Chemistry, famously faced hostility from his colleagues for years over his discovery of quasicrystals.