Tag Archives: cerium oxide nanoparticles

Nanomaterial shapes and forms affect passage through blood brain barrier (BBB)

I meant to get this published a lot sooner.

There seems to be a lot of excitement about this research. I got an embargoed press release further in advance than usual and now the embargo is lifted, it’s everywhere except, at the time of this writing (0920 PDT July 6, 2021), on the publisher’s (Proceedings of the National Academy of Sciences [PNAS]) website.

A July 5, 2021 news item on Medical Express announces the news,

Nanomaterials found in consumer and health-care products can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape—creating potential neurological impacts that could be both positive and negative, a new study reveals.

A July 5, 2021 University of Birmingham press release (also on EurekAlert), which originated the news item, delves into the details,

Scientists found that metal-based nanomaterials such as silver and zinc oxide can cross an in vitro model of the ‘blood brain barrier’ (BBB) as both particles and dissolved ions – adversely affecting the health of astrocyte cells, which control neurological responses.

But the researchers also believe that their discovery will help to design safer nanomaterials and could open up new ways of targeting hard-to-reach locations when treating brain disease.

Publishing its findings today in PNAS, an international team of researchers discovered that the physiochemical properties of metallic nanomaterials influence how effective they are at penetrating the in vitro model of the blood brain barrier and their potential levels of toxicity in the brain.

Higher concentration of certain shapes of silver nanomaterials and zinc oxide may impair cell growth and cause increased permeability of the BBB, which can lead to the BBB allowing easier brain access to these compounds.

The BBB plays a vital role in brain health by restricting the passage of various chemical substances and foreign molecules into the brain from surrounding blood vessels.

Impaired BBB integrity compromises the health of the central nervous system and increased permeability to foreign substances may eventually cause damage to the brain (neurotoxicity).

Study co-author Iseult Lynch, Professor of Environmental Nanosciences at the University of Birmingham, commented: “We found that silver and zinc oxide nanomaterials, which are widely used in various daily consumer and health-care products, passed through our in vitro BBB model, in the form of both particles and dissolved ions.

“Variation in shape, size and chemical composition can dramatically influence nanomaterials penetration through the (in vitro) blood brain barrier. This is of paramount importance for tailored medical application of nanomaterials – for example targeted delivery systems, bioimaging and assessing possible risks associated with each type of metallic nanomaterial.”

The BBB is a physical barrier composed of a tightly packed layer of endothelial cells surrounding the brain which separates the blood from the cerebrospinal fluid allowing the transfer of oxygen and essential nutrients but preventing the access of most molecules.

Recent studies found nanomaterials such as zinc oxide can accumulate on the brain side of the in vitro BBB in altered states which can affect neurological activity and brain health. Inhaled, ingested, and dermally-applied nanomaterials can reach the blood stream and a small fraction of these may cross the BBB – impacting on the central nervous system.

The researchers synthesised a library of metallic nanomaterials with different particle compositions, sizes, and shapes – evaluating their ability to penetrate the BBB using an in vitro BBB model, followed by assessment of their behaviour and fate in and beyond the model BBB.

Co-author Zhiling Guo, a Research Fellow at the University of Birmingham, commented: “”Understanding these materials’ behaviour once past the blood brain barrier is vital for evaluating the neurological effects arising from their unintentional entry into the brain. Neurotoxicity potential is greater in some materials than others, due to the different ways their shapes allow them to move and be transported.”

The research team tested varied sizes of cerium oxide and iron oxide, along with zinc oxide and four different shapes of silver – spherical (Ag NS), disc-like (Ag ND), rod-shaped (Ag NR) and nanowires (Ag NW).

Zinc oxide slipped through the in vitro BBB with the greatest ease. The researchers found spherical and disc-like silver nanomaterials underwent different dissolution regimes – gradually transforming to silver-sulfur compounds within the BBB, creating ‘easier’ entry pathways.

Zinc oxide is used as a bulking agent and a colorant. In over-the-counter drug products, it is used as a skin protectant and a sunscreen – reflecting and scattering UV radiation to help reduce or prevent sunburn and premature aging of the skin. Silver is used in cosmetic and skincare products such as anti-aging creams.

There’s still a long way to go with this research. For anyone who’s unfamiliar with the term ‘in vitro’, the rough translation is ‘in glass’ meaning test tubes, petri dishes, etc. are used. Even though the research paper has been peer-reviewed (not a perfect process), once it becomes available there will be added scrutiny from scientists with regard to how the research was conducted and whether or not the conclusions drawn are reasonable. One more question should also be asked, are the results reproducible by other scientists?

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

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model by Zhiling Guo, Peng Zhang, Swaroop Chakraborty, Andrew J Chetwynd, Fazel Abdolahpur Monikh, Christopher Stark, Hanene Ali-Boucetta, Sandra Wilson, Iseult Lynch, and Eugenia Valsami-Jones. PNAS 118 (28) e2105245118 DOI: https://doi.org/10.1073/pnas.2105245118 Published: July 13, 2021

This paper appears to be open access.

Soybeans and nanoparticles

They seem ubiquitous today but there was a time when hardly anyone living in Canada  knew much about soybeans.  There’s a good essay about soybeans and their cultivation in Canada by Erik Dorff for Statistics Canada, from Dorff’s soybean essay,

Until the mid-1970s, soybeans were restricted by climate primarily to southern Ontario. Intensive breeding programs have since opened up more widespread growing possibilities across Canada for this incredibly versatile crop: The 1.2 million hectares of soybeans reported on the Census of Agriculture in 2006 marked a near eightfold increase in area since 1976, the year the ground-breaking varieties that perform well in Canada’s shorter growing season were introduced.

Soybeans have earned their popularity, with the high-protein, high-oil beans finding use as food for human consumption, animal rations and edible oils as well as many industrial products. Moreover, soybeans, like all legumes, are able to “fix” the nitrogen the plants need from the air. This process of nitrogen fixation is a result of a symbiotic interaction between bacteria microbes that colonize the roots of the soy plant and are fed by the plant. In return, the microbes take nitrogen from the air and convert it into a form the plant can use to grow.

This means legumes require little in the way of purchased nitrogen fertilizers produced from expensive natural gas-a valuable property indeed.

Until reading Dorff’s essay, I hadn’t early soybeans had been introduced to the Canadian agricultural sector,

While soybeans arrived in Canada in the mid 1800s-with growing trials recorded in 1893 at the Ontario Agricultural College-they didn’t become a commercial oilseed crop in Canada until a crushing plant was built in southern Ontario in the 1920s, about the same time that the Department of Agriculture (now Agriculture and Agri-Food Canada) began evaluating soybean varieties suited for the region. For years, soybeans were being grown in Canada but it wasn’t until the Second World War that Statistics Canada began to collect data showing the significance of the soybean crop, with 4,400 hectares being reported in 1941. In fact, one year later the area had jumped nearly fourfold, to 17,000 hectares…

As fascinating as I find this history, this bit about soybeans and their international importance explain why research about soyboans and nanoparticles is of wide interest (from Dorff’s essay),

The soybean’s valuable characteristics have propelled it into the agricultural mix in many parts of the world. In 2004, soybeans accounted for approximately 35% of the total harvested area worldwide of annual and perennial oil crops according to the Food and Agriculture Organization of the United Nations (FAO) but only four countries accounted for nearly 90% of the production with Canada in seventh place at 1.3% (Table 2). Soymeal-the solid, high-protein material remaining after the oil has been extracted during crushing-accounts for over 60% of world vegetable and animal meal production, while soybean oil accounts for 20% of global vegetable oil production.

There’s been a recent study on the impact of nanoparticles on soybeans at the University of California at Santa Barbara (UC Santa Barbara) according to an Aug. 20, 2012 posting by Alan on the Science Business website, (h/t to Cientifica),

Researchers from University of California in Santa Barbara found manufactured nanoparticles disposed after manufacturing or customer use can end up in agricultural soil and eventually affect soybean crops. Findings of the team that includes academic, government, and corporate researchers from elsewhere in California, Texas, Iowa, New York, and Korea appear online today in the Proceedings of the National Academy of Sciences.

The research aimed to discover potential environmental implications of new industries that produce nanomaterials. Soybeans were chosen as test crops because their prominence in American agriculture — it is the second largest crop in the U.S. and the fifth largest crop worldwide — and its vulnerability to manufactured nanomaterials. The soybeans tested in this study were grown in greenhouses.

The Aug. 20, 2012 UC Santa Barbara press release has additional detail abut why the research was undertaken,

“Our society has become more environmentally aware in the last few decades, and that results in our government and scientists asking questions about the safety of new types of chemical ingredients,” said senior author Patricia Holden, a professor with the Bren School [UC Santa Barbara’s Bren School of Environmental Science & Management]. “That’s reflected by this type of research.”

Soybean was chosen for the study due to its importance as a food crop –– it is the fifth largest crop in global agricultural production and second in the U.S. –– and because it is vulnerable to MNMs [manufactured nanomaterials]. The findings showed that crop yield and quality are affected by the addition of MNMs to the soil.

The scientists studied the effects of two common nanoparticles, zinc oxide and cerium oxide, on soybeans grown in soil in greenhouses. Zinc oxide is used in cosmetics, lotions, and sunscreens. Cerium oxide is used as an ingredient in catalytic converters to minimize carbon monoxide production, and in fuel to increase fuel combustion. Cerium can enter soil through the atmosphere when fuel additives are released with diesel fuel combustion.

The zinc oxide nanoparticles may dissolve, or they may remain as a particle, or re-form as a particle, as they are processed through wastewater treatment. At the final stage of wastewater treatment there is a solid material, called biosolids, which is applied to soils in many parts of the U.S. This solid material fertilizes the soil, returning nitrogen and phosphorus that are captured during wastewater treatment. This is also a point at which zinc oxide and cerium oxide can enter the soil.

The scientists noted that the EPA requires pretreatment programs to limit direct industrial metal discharge into publicly owned wastewater treatment plants. However, the research team conveyed that “MNMs –– while measurable in the wastewater treatment plant systems –– are neither monitored nor regulated, have a high affinity for activated sludge bacteria, and thus concentrate in biosolids.”

The authors pointed out that soybean crops are farmed with equipment powered by fossil fuels, and thus MNMs can also be deposited into the soil through exhaust.

The study showed that soybean plants grown in soil that contained zinc oxide bioaccumulated zinc; they absorbed it into the stems, leaves, and beans. Food quality was affected, although it may not be harmful to humans to eat the soybeans if the zinc is in the form of ions or salts, in the plants, according to Holden.

In the case of cerium oxide, the nanoparticles did not bioaccumulate, but plant growth was stunted. Changes occurred in the root nodules, where symbiotic bacteria normally accumulate and convert atmospheric nitrogen into ammonium, which fertilizes the plant. The changes in the root nodules indicate that greater use of synthetic fertilizers might be necessary with the buildup of MNMs in the soil.

At this point, the researchers don’t know how zinc oxide nanoparticles and cerium oxide nanoparticles currently used in consumer products and elsewhere are likely to affect agricultural lands. The only certainty is that these nanoparticles are used in consumer goods and, according to Holden, they are entering agricultural soil.

The citation for the article,

Soybean susceptibility to manufactured nanomaterials with evidence for food quality and soil fertility interruption by John H. Priester, Yuan Ge, Randall E. Mielke, Allison M. Horst Shelly Cole Moritz, Katherine Espinosa, Jeff Gelb, Sharon L. Walker, Roger M. Nisbet, Youn-Joo An, Joshua P. Schimel, Reid G. Palmer, Jose A. Hernandez-Viezcas, Lijuan Zhao, Jorge L. Gardea-Torresdey, Patricia A. Holden. Published online [Proceedings of the National Academy of Sciences {PNAS}] before print August 20, 2012, doi: 10.1073/pnas.1205431109

The article is open access and available here.


Where do all those particles go or what does degradable mean at the nanoscale?

Scientists at Switzerland’s ETH Zurich (Swiss Federal Institute of Technology Zurich) note that cerium oxide nanoparticles do not degrade. From the May 21, 2012 article by Simone Ulmer on the ETH Zurich website,

Tiny particles of cerium oxide do not burn or change in the heat of a waste incineration plant. They remain intact on combustion residues or in the incineration system, as a new study by researchers from ETH Zurich reveals.

Over 100 million tons of waste are incinerated worldwide every year. Due to the increasing use of nanoparticles in construction materials, paints, textiles and cosmetics, for instance, nanoparticles also find their way into incineration plants. What happens to them there, however, had not been investigated until now. Three ETH-Zurich teams from fields of chemistry and environmental engineering thus set about finding out what happens to synthetic nano-cerium oxide during the incineration of refuse in a waste incineration plant. Cerium oxide itself is a non-toxic ceramic material, not biologically degradable and a common basic component in automobile catalytic converters and diesel soot filters.

Here’s their reasoning (from Ulmer’s article),

Experts fear that non-degradable nanomaterials might be just as harmful for humans and the environment as asbestos. As yet, however, not enough is known about the properties of nanomaterials (see ETH Life, 25 March 2010). One thing is for sure: they differ greatly from larger particles of the same material. Nanoparticles are more mobile and have a different surface structure. Knowledge of these properties is important with the increasing use of nanomaterials as, as they are transferred through incineration plants or sewage, and as they are absorbed by people in food (see ETH Life, 15 July 2008) and perhaps even through the skin and respiration, and can thus enter the body. [emphases mine]

Recent research suggests that there are many, many naturally occurring nanoparticles which we and other living beings have been innocently ingesting for millenia as noted in my Feb. 9, 2012 posting and my Nov. 24, 2011 posting. More recently, Dr. Andrew Maynard at his 2020 Science blog posted about carbon nanoparticles, which are  ubiquitous. From Andrew’s May 19, 2012 posting,

This latest paper was published in the journal Science Progress a few weeks ago, and analyzes the carbon nanoparticle content of such everyday foods as bread, caramelized sugar, corn flakes and biscuits.  The authors found that products containing caramelized sugar – including baked goods such as bread – contained spherical carbon nanoparticles in the range 4 – 30 nm (with size being associated with the temperature of caramelization).

Getting back to the cerium oxide project, here’s what the Swiss scientists found (from Ulmer’s article),

The researchers’ tests revealed that cerium oxide does not change significantly during incineration. The fly-ash separation devices proved extremely efficient: the scientists did not find any leaked cerium oxide nanoparticles in the waste incineration plant’s clean gas. That said, the nanoparticles remained loosely bound to the combustion residues in the plant and partially in the incineration system, too. The fly ash separated from the flue gas also contained cerium oxide nanoparticles.

Nowadays, combustion residues – and thus the nanoparticles bound to them – end up on landfills or are reprocessed to extract copper or aluminium, for instance. The researchers see a need for action here. “We have to make sure that new nanoparticles don’t get into the water and food cycle via landfills or released into the atmosphere through further processing measures,” says Wendelin Stark, head of the study and a professor of chemical engineering at ETH Zurich. Moreover, the fact that nanoparticles that could be inhaled if inadequate protection is worn might be present in the incineration system needs to be taken into consideration during maintenance work.

I have a couple questions for the researchers. First, is nanoscale cerium dioxide dangerous and do you have any studies?  Second, does anything ever degrade? As I recall (dimly), matter cannot be destroyed. Are they trying to break down the nanoscale cerium oxide to a smaller scale? And, what would the impact be then?

All in all, this is very interesting research to me as it has raised some questions in a way I had not previously considered. Thanks to Nanowerk where I found the May 24, 2012 news item that alerted me to the article.