Tag Archives: Iseult Lynch

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.

A library of properties for nanomaterials

Researchers at the University of Birmingham (UK) announced the development of a library of nanomaterial properties according to a June 8, 2021 news item on Nanowerk (Note: Links have been removed),

Researchers have developed a ‘library of properties’ to help identify the environmental impact of nanomaterials faster and more cost effectively.

Whilst nanomaterials have benefited a wide range of industries and revolutionized everyday life, there are concerns over potential adverse effects—including toxic effects following accumulation in different organs and indirect effects from transport of co-pollutants.

The European Union H2020-funded NanoSolveIT project is developing a ground-breaking computer-based Integrated Approach to Testing and Assessment (IATA) for the environmental health and safety of nanomaterials.

A June 8, 2021 University of Birmingham press release (also on EurekAlert) spells out the details,

Over the last two years, researchers from the University of Birmingham have worked with experts at NovaMechanics, in Nicosia, Cyprus to develop a decision support system in the form of both stand-alone open software and a Cloud platform.

The team has developed a freely available cloud library containing full physicochemical characterisation of 69 nanomaterials, plus calculated molecular descriptors to increase the value of the available information, details of which are published in NanoImpact. [link and citation follow]

Professor Iseult Lynch, from the University of Birmingham commented: “One of the limitations to widespread application of computer-based approaches is the lack of large well-organised high-quality datasets, or of data with adequate metadata that will allow dataset interoperability and their combination to create larger datasets.”

“Making the library of calculated and experimental descriptors available to the community, along with the detailed description of how they were calculated is a key first step towards filling this datagap.”

Development of the cloud-based nanomaterials library is the fifth freely available web-based application that the project has delivered.

Antreas Afantitis, from NovaMechanics, commented: “Over the last two years, this project has already presented some very impressive results with more than 30 publications, making NanoSolveIT one of the most active projects in the nanomaterials safety and informatics space.”

Concerns about nanomaterials are also arising as risk assessment is lagging behind product development, mainly because current approaches to assessing exposure, hazard and risk are expensive and time-consuming, and frequently involve testing in animal models. The NanoSolveIT project aspires to address these challenges.

The latest development aims to enrich our knowledge of nanomaterials properties and the link from property to (cytotoxic) effect. The enriched dataset contains over 70 descriptors per nanomaterial.

The dataset was used to develop a computer-based workflow to predict nanomaterials’ effective surface charge (zeta-potential) based on a set of descriptors that can be used to help design and produce safer and more functional nanomaterials.

The resulting predictive read-across model has been made publicly and freely available as a web service through the Horizon 2020 (H2020) NanoCommons project (http://enaloscloud.novamechanics.com/nanocommons/mszeta/ ) and via the H2020 NanoSolveIT Cloud Platform (https://mszeta.cloud.nanosolveit.eu/ ) to ensure accessibility to the community and interested stakeholders.

In addition, the full data set, ready for further computational modeling, is available through the NanoPharos database, as the project consortium supports the FAIR data principles – committing to making its data Findable, Accessible, Interoperable and Re-usable.

I quite like this image of how the scales are illustrated (BTW, you can find NanoSolveIT here the NanoCommons project [closing date May 15, 2021] here, and NovaMechanics here)

Scales of descriptors – from whole nanoparticle to unit cell to individual atoms Courtesy University of Birmingham and NanoSolveIT

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

Computational enrichment of physicochemical data for the development of a ζ-potential read-across predictive model with Isalos Analytics Platform by Anastasios G. Papadiamantis, Antreas Afantitis, Andreas Tsoumanis, Eugenia Valsami-Jones, Iseult Lynch, Georgia Melagraki. NanoImpact Volume 22, April 2021, 100308 DOI: https://doi.org/10.1016/j.impact.2021.100308 Available online 18 March 2021

This paper is open access.

Nanosafety Cluster newsletter—excerpts from the Spring 2016 issue

The European Commission’s NanoSafety Cluster Newsletter (no.7) Spring 2016 edition is some 50 pp. long and it provides a roundup of activities and forthcoming events. Here are a few excerpts,

“Closer to the Market” Roadmap (CTTM) now finalised

Hot off the press! the Cluster’s “Closer to the Market” Roadmap (CTTM)  is  a  multi-dimensional,  stepwise  plan  targeting  a framework to deliver safe nano-enabled products to the market. After some years of discussions, several consultations of a huge number of experts in the nanosafety-field, conferences at which the issue of market implementation of nanotechnologies was talked  about,  writing  hours/days,  and  finally  two public consultation rounds, the CTTM is now finalized.

As stated in the Executive Summary: “Nano-products and nano-enabled applications need a clear and easy-to-follow human and environmental safety framework for the development along the innovation chain from initial idea to market and beyond that facilitates  navigation  through  the  complex  regulatory and approval processes under which different product categories fall.

Download it here, and get involved in its implementation through the Cluster!
Authors: Andreas Falk* 1, Christa Schimpel1, Andrea Haase3, Benoît Hazebrouck4, Carlos Fito López5, Adriele Prina-Mello6, Kai Savolainen7, Adriënne Sips8, Jesús M. Lopez de Ipiña10, Iseult Lynch11, Costas Charitidis12, Visser Germ13

NanoDefine hosts Synergy Workshop with NSC projects

NanoDefine  organised  the  2nd Nanosafety  Cluster  (NSC)  Synergy Workshop  at  the  Netherlands  House  for Education  and  Research  in Brussels  on  2nd  February  2016. The  aim  was  to  identify  overlaps and synergies existing between different projects that could develop into
outstanding cooperation opportunities.

One central issue was the building of a common ontology and a European framework for data management and analysis, as planned within eNanoMapper, to facilitate a closer interdisciplinary collaboration between  NSC projects and to better address the need for proper data storage, analysis and sharing (Open Access).

Unexpectedly, there’s a Canadian connection,

Discovering protocols for nanoparticles: the soils case
NanoFASE WP7 & NanoSafety Cluster WG3 Exposure

In NanoFASE, of course, we focus on the exposure to nanomaterials. Having consistent and meaningful protocols to characterize the fate of nanomaterials in different environments is therefore of great interest to us. Soils and sediments are in this respect very cumbersome. Also in the case of conventional chemicals has the development of  protocols for fate description in terrestrial systems been a long route.

The special considerations of nanomaterials make this job even harder. For instance, how does one handle the fact that the interaction between soils and nanoparticles is always out of equilibrium? How does one distinguish between the nanoparticles that are still mobile and those that are attached to soil?

In the case of conventional chemicals, a single measurement of a filtered soil suspension often suffices to find the mobile fraction, as long one is sure that equilibrium has been attained. Equilibrium never occurs in the case of  nanoparticles, and the distinction between attached/suspended particles is analytically less clear to do.

Current activity in NanoFASE is focusing at finding protocols to characterize this interaction. Not only does the protocol have to provide meaningful parameters that can be used, e.g. in modelling, but also the method itself should be fast and cheap enough so that a lot of data can be collected in a reasonable amount of time. NanoFASE is  in a good position to do this, because of its focus on fate and because of the many international collaborators.

For  instance,  the Swedish  Agricultural  University (Uppsala)  is  collaborating  with  McGill  University (Montreal, Canada [emphasis mine]), an advisory partner to NanoFASE, in developing the OECD [Organization for Economic Cooperation and Development] protocol for column tests (OECD test nr 312:  “Leaching in soil columns”). The effort is led by Yasir Sultan from Environment Canada and by Karlheinz Weinfurtner from the Frauenhofer institute in Germany. Initial results show the transport of nanomaterials in soil columns to be very limited.

The OECD protocol therefore does not often lead to measurable breakthrough curves that can be modelled to provide information about  nanomaterial  mobility  in  soils  and  most  likely  requires adaptations  to  account  for  the  relatively  low mobility  of  typical pristine nanomaterials.

OECD 312 prescribes to use 40 cm columns, which is most likely too long to show a breakthrough in the case of nanoparticles. Testing in NanoFASE will therefore focus on working with shorter columns and also investigating the effect of the flow speed.

The progress and the results of this action will be reported on our website (www.nanofase.eu).

ENM [engineered nanomaterial] Transformation in and Release from Managed Waste Streams (WP5): The NanoFASE pilot Wastewater Treatment Plant is up and running and producing sludge – soon we’ll be dosing with nanoparticles to test “real world” aging.

Now, wastewater,

ENM [engineered nanomaterial] Transformation in and Release from Managed Waste Streams (WP5): The NanoFASE pilot Wastewater Treatment Plant is up and running and producing sludge – soon we’ll be dosing with nanoparticles to test “real world” aging.

WP5 led by Ralf Kaegi of EAWAG [Swiss Federal Institute of Aquatic Science and Technology] (Switzerland) will establish transformation and release rates of ENM during their passage through different reactors. We are focusing on wastewater treatment plants (WWTPs), solid waste and dedicated sewage sludge incinerators as well as landfills (see figure below). Additionally, lab-scale experiments using pristine and well characterized materials, representing the realistic fate relevant forms at each stage, will allow us to obtain a mechanistic understanding of the transformation processes in waste treatment reactors. Our experimental results will feed directly into the development of a mathematical model describing the transformation and transfer of ENMs through the investigated reactors.

I’m including this since I’ve been following the ‘silver nanoparticle story’ for some time,

NanoMILE publication update: NanoMILE on the air and on the cover

Dramatic  differences  in  behavior  of  nano-silver during  the  initial  wash  cycle  and  for  its  further dissolution/transformation potential over time depending on detergent composition and form.

In an effort to better relate nanomaterial aging procedures to those which they are most likely to undergo during the life cycle of nano-enhanced products, in this paper we describe the various transformations which are possible when exposing Ag engineered nanoparticles (ENPs) to a suite of commercially available washing detergents (Figure 1). While Ag ENP transformation and washing of textiles has received considerable attention in recent years, our study is novel in that we (1) used several commercially available detergents allowing us to estimate the various changes possible in individual homes and commercial washing settings; (2) we have continued  method  development  of  state  of  the  art nanometrology techniques, including single particle ICP-MS, for the detection and characterization of ENPs in complex media; and (3) we were able to provide novel additions to the knowledge base of the environmental nanotechnology research community both in terms of the analytical methods (e.g. the first time ENP aggregates have been definitively analyzed via single particle ICP-MS) and broadening the scope of “real world” conditions that should be considered when understanding AgENP through their life cycle.

Our findings, which were recently published in Environmental Science and Toxicology (2015, 49: 9665), indicate that the washing detergent chemistry causes dramatic differences in ENP behavior during the initial wash cycle and has ramifications for the dissolution/transformation potential of the Ag ENPs over time (see Figure 2). The use of silver as an  antimicrobial  treatment  in  textiles  continues  to garner  considerable  attention.  Last  year  we  published  a manuscript in ACS Nano that considered how various silver treatments to textiles (conventional and nano) both release  nano-sized  material  after  the  wash  cycle  with  similar chemical  characteristics.  That  study  essentially conveyed that multiple silver treatments would become more similar through the product life cycle. Our newest  work expands this by investigating one silver ENP under various washing conditions thereby creating more varied silver products as an end result.

Fascinating stuff if you’ve been following the issues around nanotechnology and safety.

Towards the end of the newsletter on pp. 46-48, they list opportunities for partnerships, collaboration, and research posts and they list websites where you can check out job opportunities. Good Luck!