Tag Archives: Bengt Fadeel

Human lung enzyme can degrade graphene

Caption: A human lung enzyme can biodegrade graphene. Credit: Fotolia Courtesy: Graphene Flagship

The big European Commission research programme, Grahene Flagship, has announced some new work with widespread implications if graphene is to be used in biomedical implants. From a August 23, 2018 news item on ScienceDaily,

Myeloperoxidase — an enzyme naturally found in our lungs — can biodegrade pristine graphene, according to the latest discovery of Graphene Flagship partners in CNRS, University of Strasbourg (France), Karolinska Institute (Sweden) and University of Castilla-La Mancha (Spain). Among other projects, the Graphene Flagship designs based like flexible biomedical electronic devices that will interfaced with the human body. Such applications require graphene to be biodegradable, so our body can be expelled from the body.

An August 23, 2018 Grapehene Flagship press release (mildly edited version on EurekAlert), which originated the news item, provides more detail,

To test how graphene behaves within the body, researchers analysed how it was broken down with the addition of a common human enzyme – myeloperoxidase or MPO. If a foreign body or bacteria is detected, neutrophils surround it and secrete MPO, thereby destroying the threat. Previous work by Graphene Flagship partners found that MPO could successfully biodegrade graphene oxide.

However, the structure of non-functionalized graphene was thought to be more resistant to degradation. To test this, the team looked at the effects of MPO ex vivo on two graphene forms; single- and few-layer.

Alberto Bianco, researcher at Graphene Flagship Partner CNRS, explains: “We used two forms of graphene, single- and few-layer, prepared by two different methods in water. They were then taken and put in contact with myeloperoxidase in the presence of hydrogen peroxide. This peroxidase was able to degrade and oxidise them. This was really unexpected, because we thought that non-functionalized graphene was more resistant than graphene oxide.”

Rajendra Kurapati, first author on the study and researcher at Graphene Flagship Partner CNRS, remarks how “the results emphasize that highly dispersible graphene could be degraded in the body by the action of neutrophils. This would open the new avenue for developing graphene-based materials.”

With successful ex-vivo testing, in-vivo testing is the next stage. Bengt Fadeel, professor at Graphene Flagship Partner Karolinska Institute believes that “understanding whether graphene is biodegradable or not is important for biomedical and other applications of this material. The fact that cells of the immune system are capable of handling graphene is very promising.”

Prof. Maurizio Prato, the Graphene Flagship leader for its Health and Environment Work Package said that “the enzymatic degradation of graphene is a very important topic, because in principle, graphene dispersed in the atmosphere could produce some harm. Instead, if there are microorganisms able to degrade graphene and related materials, the persistence of these materials in our environment will be strongly decreased. These types of studies are needed.” “What is also needed is to investigate the nature of degradation products,” adds Prato. “Once graphene is digested by enzymes, it could produce harmful derivatives. We need to know the structure of these derivatives and study their impact on health and environment,” he concludes.

Prof. Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship, and chair of its management panel added: “The report of a successful avenue for graphene biodegradation is a very important step forward to ensure the safe use of this material in applications. The Graphene Flagship has put the investigation of the health and environment effects of graphene at the centre of its programme since the start. These results strengthen our innovation and technology roadmap.”

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

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase by Dr. Rajendra Kurapati, Dr. Sourav P. Mukherjee, Dr. Cristina Martín, Dr. George Bepete, Prof. Ester Vázquez, Dr. Alain Pénicaud, Prof. Dr. Bengt Fadeel, Dr. Alberto Bianco. Angewandte Chemie https://doi.org/10.1002/anie.201806906 First published: 13 July 2018

This paper is behind a paywall.

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

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),


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. …


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. …


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. …


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.  …


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). …


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. …


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. …


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. …


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. …


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. …


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. …


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. …


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. …


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. …


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.  …


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. …


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. …


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.  …


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). …


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. …


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). …


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?

The memristor rises; commercialization and academic research in the US; carbon nanotubes could be made safer than we thought

In 2008, two memristor papers were published in Nature and Nature Nanotechnology, respectively. In the first (Nature, May 2008 [article still behind a paywall], a team at HP Labs claimed they had proved the existence of memristors (a fourth member of electrical engineering’s ‘Holy Trinity of the capacitor, resistor, and inductor’). In the second paper (Nature Nanotechnology, July 2008 [article still behind a paywall]) the team reported that they had achieved engineering control.

I mention this because (a) there’s some new excitement about memristors and (b) I love the story (you can read my summary of the 2008 story here on the Nanotech Mysteries wiki).

Unbeknownst to me in 2008, there was another team, located in Japan, whose work  on slime mould inspired research by a group at the University of California San Diego (UC San Diego)  which confirmed theorist Leon Chua’s (he first suggested memristors existed in 1971) intuition that biological organisms used memristive systems to learn. From an article (Synapse on a Chip) by Surf daddy Orca on the HPlus magazine site,

Experiments with slime molds in 2008 by Tetsu Saisuga at Hokkaido University in Sapporo sparked additional research at the University of California, San Diego by Max Di Ventra. Di Ventra was familiar with Chua’s work and built a memristive circuit that was able to learn and predict future signals. This ability turns out to be similar to the electrical activity involved in the ebb and flow of potassium and sodium ions across cellular membranes: synapses altering their response according to the frequency and strength of signals. New Scientist reports that Di Ventra’s work confirmed Chua’s suspicions that “synapses were memristors.” “The ion channel was the missing circuit element I was looking for,” says Chua, “and it already existed in nature.”

Fast forward to 2010 and a team at the University of Michigan led by Dr. Wei Lu showing how synapses behave like memristors (published in Nano Letters, DOI: 10.1021/nl904092h [article behind paywall]). (Fromthe  HPlus site article)

Scientific American describes a US military-funded project that is trying to use the memristor “to make neural computing a reality.” DARPA’s Systems of Neuromorphic Adaptive Plastic Scalable Electronics Program (SyNAPSE) is funded to create “electronic neuromorphic machine technology that is scalable to biological levels.”

I’m not sure if the research in Michigan and elsewhere is being funded by DARPA (the US Dept. of Defense’s Defense Advanced Research Project Agency) although it seems likely.

In the short term, scientists talk about energy savings (no need to reboot your computer when you turn it back on). In the longer term, they talk about hardware being able to learn. (Thanks to the Foresight Institute for the latest update on the memristor story and the pointer to HPlus.) Do visit the HPlus site as there are some videos of scientists talking about memristors and additional information (there’s yet another team working on research that is tangentially related).

Commercializing academic research in US

Thanks to Dave Bruggeman at the Pasco Phronesis blog who’s posted some information about a White House Request for Information (RFI) on commercializing academic research. This is of particular interest not just because of the discussion about innovation in Canada but also because the US National Nanotechnology Initiative’s report to PCAST (President’s Council of Advisors on Science and Technology, my comments about the webcast of the proceedings here). From the Pasco Phronesis posting about the NNI report,

While the report notes that the U.S. continues to have a strong nanotechnology sector and corresponding support from the government. However, as with most other economic and research sectors, the rest of the world is catching up, or spending enough to try and catch up to the United States.

According to the report, more attention needs to be paid to commercialization efforts (a concern not unique to nanotechnology).

I don’t know how long the White House’s RFI has been under development but it was made public at the end of March 2010 just weeks after the latest series of reports to PCAST. As for the RFI itself, from the Pasco Phronesis posting about it,

The RFI questions are organized around two basic concerns:

  • Seeking ideas for supporting the commercialization and diffusion of university research. This would include best practices, useful models, metrics (with evidence of their success), and suggested changes in federal policy and/or research funding. In addition, the RFI is interested in how commercialization ecosystems can be developed where none exist.
  • Collecting data on private proof of concept centers (POCCs). These entities seek to help get research over the so-called “Valley of Death” between demonstrable research idea and final commercial product. The RFI is looking for similar kinds of information as for commercialization in general: best practices, metrics, underlying conditions that facilitate such centers.

I find the news of this RFI a little surprising since I had the impression that commercialization of academic research in the US is far more advanced than it is here in Canada. Mind you, that impression is based on a conversation I had with a researcher a year ago who commented that his mentor at a US university rolled out more than 1 start up company every year. As I understand it researchers in Canada may start up one or two companies in their career but never a series of them.

Carbon nanotubes, is exposure ok?

There’s some new research which suggests that carbon nanotubes can be broken down by an enzyme. From the news item on Nanowerk,

A team of Swedish and American scientists has shown for the first time that carbon nanotubes can be broken down by an enzyme – myeloperoxidase (MPO) – found in white blood cells. Their discoveries are presented in Nature Nanotechnology (“Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation”) and contradict what was previously believed, that carbon nanotubes are not broken down in the body or in nature. The scientists hope that this new understanding of how MPO converts carbon nanotubes into water and carbon dioxide can be of significance to medicine.

“Previous studies have shown that carbon nanotubes could be used for introducing drugs or other substances into human cells,” says Bengt Fadeel, associate professor at the Swedish medical university Karolinska Institutet. “The problem has been not knowing how to control the breakdown of the nanotubes, which can caused unwanted toxicity and tissue damage. Our study now shows how they can be broken down biologically into harmless components.”

I believe they tested single-walled carbon nanotubes (CNTs) only as the person who wrote the news release seems unaware that mutil-walled CNTs also exist. In any event, this could be very exciting if this research holds up under more testing.