Tag Archives: Eugenia Valsami-Jones

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

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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

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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.

Summary of EHS studies on nanotechnology funded through Europe’s 7th Framework Programme

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I was a little shocked to see how many EHS (environment, health, and safety) projects focussed on nanotechnology that the European Union (EU) funded as part of its overarching science funding efforts, the 7th Framework Program, due to be superseded in the near future (2013)) by the Horizon 2020 program. The June 18, 2012 Nanowerk Spotlight article submitted by NanoTrust, Austrian Academy of Sciences provides the reasoning for the EU  effort (Note: I have removed footnotes.),

The Action Plan, presented by the EU Commission in 2004, envisioned integrating “the social dimension into a responsible technology development” and strengthening efforts related to “health, safety, environmental aspects and consumer protection“.

This encompassed (1) the systematic study of safety-relevant aspects at the earliest possible date, (2) integrating health- and environment-relevant aspect in research and development, (3) conducting targeted studies on toxicology and ecotoxicology and, finally, (4) adapting risk assessment approaches to nano-specific aspects in all phases of product life-cycles.

The primary goal was to improve the competitiveness of European industry. The draft presented in mid-2011 for the planned research priorities continues this strategic focus.

The EU Parliament had already discussed the Nano Action Plan developed by the Commission before the start of the current Framework Program. From the onset, the relevant parliamentary resolution called for an improved coordination with the Member States and more risk research, consideration of the precautionary principle and a deepened dialogue with citizens.

The EU Parliament clearly felt that the rules require urgent adaptations in order to adequately consider nano-risks: In the resolution of April 2009 the parliamentarians underlined the existence of a considerable “lack of information about the use and safety of nanomaterials that are already on the market”.

The overall scope of the projects on nanotechnology, materials and production (NMP) funded by the 7th RP is listed at about 3.475 mill. €. According to EU sources, about 102 mill. € were earmarked for safety aspects (nanosafety research).The comparison with the much more modest Nano-EHS-budget in the past clearly shows the change here (5th RP: about 2.5 mill. €, 6th RP 6 about 30 mill. €).

The publication from where this information was drawn is no.30 in the NanoTrust Dossier series. It was published in May 2012 (from pp. 2-6),

ENNSATOX

Title: Engineered Nanoparticle Impact on Aquatic Environments: Structure, Activity and Toxicology

Coordinator: Andrew Nelson,
Centre for Molecular Nanosciences (CMNS), School of Chemistry, University of Leeds, UK
Duration: July 2009 to July 2012
Project costs: 3,655 mill. €
EU funding: 2,816 mill. €
Homepage: www.ennsatox.eu

The goal of ENNSATOX is to investigate the environmental effects of various synthetic nanoparticles from the time of their release to their potential uptake by organisms, particularly in rivers and lakes. …

ENPRA

Title: Risk Assessment of Engineered Nanoparticles

Coordinator: Lang Tran,
Institute of Occupational Medicine (IOM), Edinburg, UK
Duration: July 2009 to July 2012
Project costs: 5,13 mill. €
EU funding: 3,7 mill. €
Homepage: www.enpra.eu

ENPRA is examining the impacts of selected and commercially used nanomaterials, whereby the different target organs (lungs, cardiovascular system, kidneys etc.) and different mechanisms of damage (see Nano Trust-Dossier 012en) are being determined. …

HINAMOX

Title: Health Impact of Engineered Metal and Metal Oxide Nanoparticles Response, Bioimaging and Distribution at Cellular and Body Level

Coordinator: Sergio E. Moya,
Centro de Investigación Cooperativa en Biomateriales (Spanien)
Duration: October 2009 to October 2012
Project costs: 2.93 mill. €
EU funding: 2.3 mill. €
Homepage: www.hinamox.eu

HINAMOX deals with the impacts of several metal-oxide nanoparticles – TiO2, ZnO, Al2O3, CeO2 etc. – on human health and on biological systems. …

InLiveTox

Title: Intestinal, Liver and Endothelial Nanoparticle Toxicity – development and evaluation of a novel tool for high-throughput data generation

Coordinator: Martha Liley,
CSEM (Centre Suisse d’Electronique et de Microtechnique SA)
Duration: May 2009 to July 2012
Project costs: 3.42 mill. €
EU funding: 2.4 mill. €
Homepage: www.inlivetox.eu

In InLiveTox, an improved in-vitro model is being developed to describe the effects of nanoparticles taken up via food, especially effects on the gastrointestinal tract and the liver.  …

MARINA

Title: Managing Risks of Nanomaterials

Coordinator: Lang Tran,
IOM (Institute of Occupational Medicine) Edinburgh, UK
Duration: November 2011 to November 2015
Project costs: 12.48 Mio. €
EU funding: 9.0 mill. €
Homepage: www.marina-fp7.eu and http://www.iom-world.org

A total of almost 50 industrial companies (including BASF) and scientific facilities are combined in the very large joint project MARINA, coordinated by the Institute of Occupational Medicine of the University of Edinburgh; other organizations that are involved in employee protection and occupational safety are also participating (FIOH/Finland, IST/Switzerland, RIVM/The Netherlands). …

ModNanoTox

Title: Modelling nanoparticle toxicity: principles, methods, novel approaches Toxicology

Coordinator: Eugenia Valsami-Jones,
Natural History Museum, London, UK
Duration: November 2011 to November 2013
Project costs: 1.28 mill. €
EU funding: 1.0 mill. €
Homepage: (under construction) lib.bioinfo.pl/projects/view/32734

The goal of ModNanoTox is to develop welldocumented models on the long-term behavior of synthetic nanoparticles in organisms and in the environment. …

NanEx

Title: Development of Exposure Scenarios for Manufactured Nanomaterials

Coordinator: Martie van Tongeren,
Institute of Occupational Medicine (IOM), Edinburgh UK
Duration: December 2009 to November 2010
Project costs: 1.01 mill. €
EU funding: 0.95 mill. €
Homepage: www.nanex-project.eu, lib.bioinfo.pl/projects/view/12016

In NanEx, a catalog of realistic scenarios is being developed for potential impacts of synthetic nanoparticles at industrial workplaces, of various uses by consumers as well as of delayed releases into the environment. …

NANODEVICE

Title: Modelling Novel Concepts, Methods and Technologies for the Production of Portable, Easy-to-Use Devices for the Measurement and Analysis of Airborne Nanoparticles in Workplace Air

Coordinator: Kai Savolainen,
Finnish Institute for Occupational Health (FIOH), Finland
Duration: April 2009 to April 2013
Project costs: 12.28 mill. €
EU funding: 9.49 mill. €
Homepage: www.nano-device.eu

Due to the lack of robust and inexpensive instruments, the nanoparticle concentrations in the air at the workplace cannot be measured at the present time. NANODEVICE is devoted to studying innovative concepts and practicable methods for identifying synthetic nanomaterials, methods that can also be used at the workplace. …

NanoFATE

Title: Nanoparticle Fate Assessment and Toxicity in the Environment

Coordinator: Klaus Svendsen,
NERC (Centre for Ecology and Hydrology),
Wallingford, UK
Duration: April 2010 to April 2014
Project costs: 3.25 mill. €
EU funding: 2.50 mill. €
Homepage: www.nanofate.eu

NanoFATE is devoted to systematically deepening our knowledge about the behavior and the fate of synthetic nanoparticles that enter the environment. …

Nanogenotox

Title: Towards a method for detecting the potential genotoxicity of nanomaterials

Coordinator: Anses – French Agency for Food, Environmental and Occupational Health Safety
Duration: March 2010 to March 2014
Project costs: 6.0 mill. € EU funding: 2.90 mill. € (as co-funding though the program
EU-Health & Consumers)
Homepage: www.nanogenotox.eu/

Nanogenotox is not directly a part of the 7th RP but rather a Joint Action, about half of which is funded by the participating European states. The task of this project is to study the gene toxicity (i.e. the damaging effect on the genetic material of organisms) of selected nanomaterials. …

NanoHouse

Title: Cycle of Nanoparticle-Based Products used in House-Coating

Coordinator: Francois Tardif,
CEA (Commissariat à l’Énergie Atomique et aux Energies Alternatives), Grenoble, Frankreich
Duration: January 2010 to July 2013
Project costs: 3.1 mill. €
EU funding: 2.4 mill. €
Homepage: www-nanohouse.cea.fr

The task of NanoHouse is to comprehensively evaluate environmentally relevant and health-related effects of nanoproducts used in house construction; the focus is on paints and coatings with TiO2- and nanosilver components, whose impacts and fates are being more closely examined. …

NanoImpactNet

Title: The European Network on the Health and Environmental Impact of Nanomaterials

Coordinator: Michael Riediker,
Institut universitaire romand der Santé au Travail, Schweiz (IST)
Duration: April 2008 to April 2012
Project costs: 3.19 mill. €
EU funding: 2.0 mill. €
Homepage: www.nanoimpactnet.eu

This large network of partner institutes from numerous countries is designed mainly to exchange information about new knowledge as well as knowledge gaps in the health- and environment-related impacts of nanoparticles. …

NanoLyse

Title: Nanoparticles in Food: Analytical Methods for Detection and Characterisation

Coordinator: Stefan Weigel,
RIKILT – Institute of Food Safety, Niederlande
Duration: January 2010 to October 2013
Project costs: 4.05 mill. €
EU funding: 2.95 mill. €
Homepage: www.nanolyse.eu

The goal of NanoLyse is to develop approved methods for analyzing synthetic nanomaterials in food and drinks. …

NANOMMUNE

Title: Comprehensive Assessment of Hazardous Effects of Engineered Nanomaterials on the Immune System Toxicology

Coordinator: Bengt Fadeel,
Karolinsk  Institutet, Stockholm
Duration: September 2008 to September 2011 (completed)
Project costs: 4.31 mill. €
EU funding: 3.36 mill. €
Homepage: www.nanommune.eu

NANOMMUNE examined the influence of synthetic nanomaterials on the immune system and their potential negative health effects. …

NanoPolyTox

Title: Toxicological impact of nanomaterials derived from processing, weathering and recycling of polymer nanocomposites used in various industrial applications

Coordinator: Socorro Vázquez-Campos,
LEITAT Technological Centre, Barcelona, Spain
Duration: May 2010 to May 2013
Project costs: 3.30 mill. €
EU funding: 2.43 mill. €
Homepage: www.nanopolytox.eu

NanoPolyTox is tasked with determining the changes in the physical and toxic properties of three different nanomaterials (nanotubes, nano-clay minerals, metal-oxide nanoparticles) that are used in combination with polymers as filling materials.  …

NanoReTox

Title: The reactivity and toxicity of engineered nanoparticles: risks to the environment and human health

Coordinator: Eugenia Valsami-Jones,
Natural History Museum, London, UK
Duration: December 2008 to December 2012
Project costs: 5.19 mill. €
EU funding: 3.19 mill. €
Homepage: www.nanoretox.eu

NanoReTox is designed to better describe the EHS-risks of synthetic nanomaterials based on new research results. …

NanoSustain

Title: Development of sustainable solutions for nanotechnology-based products based on hazard characterization and LCA

Coordinator: Rudolf Reuther,
NordMilijö AB, Sweden
Duration: May 2010 to May 2013
Project costs: 3.2 mill. €
EU funding: 2.5 mill. €
Homepage: www.nanosustain.eu

NanoSustain is designed to develop innovative solutions for all phases in dealing with nanotechnology products – up until the landfill or recycling stage. Four nanomaterials are being examined in greater detail: nano-cellulose, CNT, nano-TiO2, as well as nano-ZnO. …

NanoTransKinetics

Title: Modelling basis and kinetics of nanoparticle interaction with membranes, uptake into cells, and sub-cellular and inter-compartmental transport

Coordinator: Kenneth Dawson,
University College, Dublin, Ireland
Duration: November 2011 to November 2014
Project costs: 1.3 mill. €
EU funding: 0.99 mill. €
Homepage: www.nanotranskinetics.eu

The aim of NanoTransKinetics is to substantially improve the models used to describe biological (and therefore also toxic) interrelationships between nanoparticles and living organisms.  …

NanoValid

Title: Development of reference methods for hazard identification, risk assessment and LCA of engineered nanomaterials

Coordinator: Rudolf Reuther,
NordMiljö AB, Sweden
Duration: November 2011 to November 2015
Project costs: 13.4 mill. €
EU funding: 9.6 mill. €
Homepage: www.nanovalid.eu

The aim of NanoValid is to develop reference methods and materials to identify and assess the risks of synthetic nanomaterials in close cooperation with the similarly oriented project MARINA (see above). …

NEPHH

Title: Nanomaterials-related environmental pollution and health hazards throughout their life-cycle

Coordinator: EKOTEK S.L. (Spanien)
Duration: September 2009 to September 2012
Project costs: 3.1 mill. €
EU funding: 2.5 mill. €
Homepage: www.nephh-fp7.eu

NEPHH seeks to better estimate the environmental and health-related risks of nanostructures over the course of their use. …

NeuroNano

Title: Do nanoparticles induce neurodegenerative diseases? Understanding the origin of reactive oxidative species and protein aggregation and mis-folding phenomena in the presence of nanoparticles

Coordinator: Kenneth Dawson,
University College, Dublin, Ireland
Duration: February 2009 toFebruary 2012
Project costs: 4.8 mill. €
EU funding: 2.5 mill. €
Homepage: www.neuronano.eu

To date, the full details on the factors that allow nanoparticles to pass the blood-brain barrier are unknown15. NeuroNano examines the effect of nanoparticle size, shape and composition, along with the role of the adsorbed corona of biomolecules (see above). …

QNano

Title: A pan-european infrastructure for quality in nanomaterials safety testing

Coordinator: Kenneth Dawson,
University College, Dublin, Ireland
Duration: February 2011 to February 2015
Project costs: 9.2 mill. €
EU funding: 7.0 mill. €
Homepage: www.qnano-ri.eu

Rather than being devoted to a separate research topic, QNano is designed to interlink and support facilities that provide the necessary infrastructure for investigating and characterizing nanosubstances. …

That’s quite the list, eh?