Tag Archives: Hanene Ali-Boucetta

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.

The yin and the yang of carbon nanotubes and toxicity


Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Illustration courtesy of the University College of London (UCL). Downloaded from http://www.ucl.ac.uk/news/news-articles/0113/130115-chemistry-resolves-toxic-concerns-about-carbon-nanotubes

Researchers at the University College of London (UCL), France’s Centre national de la recherche scientifique (CNRS), and Italy’s University of Trieste have determined that carbon nanotube toxicity issues can be addressed be reducing their length and treating them chemically. From the Jan. 15,2013 news item on ScienceDaily,

In a new study, published January 15 [2013] in the journal Angewandte Chemie, evidence is provided that the asbestos-like reactivity and pathogenicity reported for long, pristine nanotubes can be completely alleviated if their surface is modified and their effective length is reduced as a result of chemical treatment.

First atomically described in the 1990s, carbon nanotubes are sheets of carbon atoms rolled up into hollow tubes just a few nanometres in diameter. Engineered carbon nanotubes can be chemically modified, with the addition of chemotherapeutic drugs, fluorescent tags or nucleic acids — opening up applications in cancer and gene therapy.

Furthermore, these chemically modified carbon nanotubes can pierce the cell membrane, acting as a kind of ‘nano-needle’, allowing the possibility of efficient transport of therapeutic and diagnostic agents directly into the cytoplasm of cells.

Among their downsides however, have been concerns about their safety profile. One of the most serious concerns, highlighted in 2008, involves the carcinogenic risk from the exposure and persistence of such fibres in the body. Some studies indicate that when long untreated carbon nanotubes are injected to the abdominal cavity of mice they can induce unwanted responses resembling those associated with exposure to certain asbestos fibres.

In this paper, the authors describe two different reactions which ask if any chemical modification can render the nanotubes non-toxic. They conclude that not all chemical treatments alleviate the toxicity risks associated with the material. Only those reactions that are able to render carbon nanotubes short and stably suspended in biological fluids without aggregation are able to result in safe, risk-free material.

Here’s a citation and link for this latest  research, from the ScienceDaily news item where you can also read the lead researcher’s comments about carbon nanotubes, safety, and unreasonable proposals to halt production,

Hanene Ali-Boucetta, Antonio Nunes, Raquel Sainz, M. Antonia Herrero, Bowen Tian, Maurizio Prato, Alberto Bianco, Kostas Kostarelos. Asbestos-like Pathogenicity of Long Carbon Nanotubes Alleviated by Chemical Functionalization. Angewandte Chemie International Edition, 2013; DOI: 10.1002/anie.201207664

The article is behind a paywall. I have mentioned long carbon nanotubes and their resemblance to asbestos fibres in several posts. The  Oct. 26, 2009 posting [scroll down about 1/3 of the way] highlights research which took place after the study where mice had carbon nanotubes injected into their bellies; in this second piece of research they inhaled the nanotubes.

ETA Jan. 21, 2013: Dexter Johnson gives context and commentary about this latest research into long multiwalled nanotubes (MWNTs) which he sums up as the answer to this question “What if you kept the MWNTs short?”  in a Jan. 18, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website)