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01 Mar
2017
Industrial workshop on safe-by-design
News Photo NanoMILE co-organizes the workshop on 24-25.04.2017 in Bilbao.



A number of H2020 funded projects are working on various aspects of the Safe-by-Design (SbD) concept and all rely upon industry to understand its meaning and how to use the tools being developed in these projects.
Disseminating this knowledge to a wider audience will help in the acceptance and uptake of SbD by companies and will also allow the projects to learn more about stakeholder needs.
A workshop that allows knowledge exchange between various SbD projects as well as listening and learning from  different stakeholder groups (industry, academia, regulators, insurance, consumers) can help adjusting research, dissemination and exploitation strategies accordingly. This ensures project outcomes and tools are relevant long after the project has officially concluded.

Click here for the workshop flyer or to registrate.

09 Feb
2017
Prize winning NanoMILE poster
News Photo At the NMSA conference in Malaga.



Susan Dekkers (RIVM) et al. were awarded the RSC Environmental Science Nano best poster Prize at the NMSA Malaga conference for the poster on The influence of redox activity of inhaled nano-sized cerium dioxide on respiratory, immune and cardiovascular effects in multiple mouse models.

 

Figure from the poster: Figure 2: Atherosclerotic plaque (red outline) in the brachiocephalic arteries of ApoE-/- mice

07 Feb
2017
Nanosafety 5-project Conference
News Photo NanoMILE final conference: New tools and approaches for nanomaterial safety assessment 7-9 Feb 2017, Malaga (Spain)



A joint final conference of the five major FP7 projects NANOSOLUTIONS, SUN, NanoMILE, GUIDEnano, and eNanoMapper.

The conference will present the main results achieved in the course of the projects fostering a discussion about their impact in the nanosafety field and possibilities for future research programmes. The conference welcomes consortium partners from the organizing projects, as well as representatives from other EU projects, industry and government, civil society and media.

More information: http://www.nmsaconference.eu/.

Abstract submission until 30/09/2016.

27 Oct
2016
Workshop on Nanomedicine & Contrast agents
News Photo A two-day Workshop on Nanomedicine & Contrast agents for PhD students in Maastricht.



On October 27-28th 2016, Nano4Imaging organizes a two-day Workshop on Nanomedicine & Contrast agents for PhD students in projects ITERM and NanoMILE. The workshop is open for participants from industry and academia, and can host another 10 participants. The workshop focusses on the clinical importance of contrast agents, as well as the current toxicological problems with many of these agents. The workshop venue is the loverly Chateau Bethlehem Teaching Hotel Maastricht.  Speakers include Prof. Jelle Barentsz (Nijmegen), Prof. Fabian Kieslsing (Aachen), Dr Iseult Lynch (Birmingham).

Draft program (12.09.2016). More info on the workshop website.

13 Sep
2016
NanoMILE- NanoSOLUTIONS workshop on High-throughput and “omics”
News Photo on 13th and 14th September in Stockholm, Sweden



        

Ambition, format, goal

10 years of investment in nanosafety science by the European Commission via Framework Programmes 6 and 7 has led to an enormous body of data and expertise on nanosafety science in Europe.  To ensure continuity of effort, and facilitate the translation from nanosafety science to standardisation, industry and regulation within Horizon2020, the flagship projects on mechanisms of nanomaterials interactions with living systems, NanoMILE and NanoSOLUTIONS organize a workshop on 13-14.09.2016, with the goal to develop a consensus paper on scientific best practice and approaches for high throughput & “omics” approaches to nanosafety assessment.  

The workshop will consist of keynote presentations followed by break-out discussion to reach consensus on selected topics, based around a prepared discussion document.  Summaries from the discussion break-out groups will be presented back to the group in plenary for final discussion.

Outputs from the workshop will be:

–        White paper & associated summary publication

–        Agreed terminology for the topic and agreed protocols and approaches

–        Agreed understanding of current limitations of the methods / approaches in terms of their applicability to different NMs classes

–        Plan for benchmarking activities and securing buy-in of projects with capabilities to achieve this.

 

This 2-day event will be followed by an EU NanoSafety Cluster meeting, at the same venue, on 14.09.2016.  Registration for the NSC meeting to Elina Drakvik (Elina.Drakvik@ttl.fi).

 

Location

Karolinska Institute in Stockholm.

 

Further information / to express interest in participating:

NanoMILE Project manager:  Mr. Tom Carney, email: t.carney@bham.ac.uk
04 Sep
2016
NanoMILE at Nano-Metrology Summer School
News Photo NanoMILE partner IUF will present the basic principles of nanotoxicology



Knowledge gained through NanoMILE  will feed IUF's presentation at the

Organized by the FP7 Project SETNanoMetro, the Summer School aims to illustrate and discuss the most recent advances in the synthesis, characterization, testing and application of nanoparticles with controlled properties.

The school is addressed to PhD students and Post-Docs with a background in Physics, Chemistry, Material Science, Regenerative Biology and Medicine.

For more detail and for registration, please see here.

15 Aug
2016
Meet NanoMILE (and others) at the NanoSafety Forum for Young Scientists
News Photo In Visby, Sweden, 15-16 September.




Nanosafety Forum
for young scientists


The NanoSafety Cluster is hosting a “Nanosafety Forum for Young Scientists”. The event will take place in Visby, Sweden, on 15-16.09.2016, complemented by opportunities to meet experts and senior scientists. Prior to the Forum for young scientists the NSC meeting will be held on the 14th.

The event is an open Forum for scientists in the nanosafety research field including scientific sessions with oral presentations from the young scientists and forward looking keynotes from established senior investigators. The goal is to exchange scientific information and visions and to enable young and senior scientists to learn to know each other.

Early bird registration at preferential rate is now extended to 30 July.
Final registration deadline is 15 August 2016.

More information at: http://www.trippus.net/nanosafetyforum2016

19 Jul
2016
Ecotoxicity testing: an overview
News Photo Environment is so diverse: how and where to start ??



Ecotoxicity testing for an environmentally safer-by-design nanotechnology industry : an overview

The environment presents a large, dynamic and highly complex arena. Unlike for human toxicity, where the focus is a single species – man, protection of wildlife needs to consider a very wide range of organism that are representative of the world’s ecology. So how and where do you start in considering possible biological effects of NMs in the environment? And, of course, the answer is not a straight forward one. It is clearly not possible to test all organisms and cover all trophic systems. For chemicals, ecotoxicity testing uses a range of representative microbes, plant, invertebrate and vertebrates for terrestrial and aquatic systems. In the world of nanotoxicology the approach is the same, although the test organisms chosen to represent phyla or classes of organisms for protection might differ to best represent the differences in fate and compartmentalisation of NMs in the environment.

 

Here, the WP6 partners present the organisms they have adopted and the reasons behind their selection as our models to study the ecotoxicology of NMs.

22 Jun
2016
NanoMILE & applied nanoSafety at IT 2016
News Photo From nanosafety research to operational tools for the nanotechnology industry



Industrial Technologies 2016 (22-24.06.2016, Amsterdam) is the largest networking conference in the field of new production technologies, materials, nanotechnology, biotechnology and digitalisation in Europe, with more than 200 speakers and 1500 attendees.


             

On the first afternoon, the NanoMILE partner EU-VRi organized a workshop on "Nanosafety: From research to implementation of Risk Management and Safe Innovation in the nanotechnology industry". The workshop presented, illustrated and discussed, through recent and running R&D projects and initiatives, ways and solutions to bridge the gap between scientific knowledge and the market. At this workshop, EU-VRi presented outputs from nanosafety research, NanoMILE and other NanoSafety Cluster projects, that will lead to operational tools for the nanotechnology industry.

Please find here the agenda of the workshop.

Please find here the presentations of the workshop.


13 Jun
2016
Attana (QCM) biosensor networking meeting
News Photo The meeting brought together scientists and users at the University of Westminster.



Quartz crystal microbalance (QCM) biosensors, such as the Attana systems, allow the study of drug-target interactions and are an important tool in the drug discovery pipeline.
Biomolecules ranging from proteins, nucleic acids, carbohydrates to lipids and moieties of vastly different sizes, from peptides to cells can be studied using QCM. This versatile technnology has many applications and has been used in applications ranging from cancer therapies to nanotechnologies and more recently to study drug interactions at the cell surface.

During the event you will learn about some of the recent applications and
developments by expert users of the Attana Biosensor equipment. The day will include presentations showcasing research from users in academia and industry.
There will be round table discussions on different applications of the technology.
This is a chance for you to network with experienced users and to learn about potential applications of QCM technology. This event will provide a great opportunity for existing and potential users to share ideas and to consider possible collaborative ventures.
To facilitate the networking opportunities, delegates are encouraged to bring posters outlining their research interests.

For more detail and for registration, please see the agenda or click here.

Please find here a poster presented by Attana at the meeting.

07 Jun
2016
Interactions between nanoparticles and biomolecules unveiled
News Photo NanoMILE outlines the nature of interactions between nanoparticles and a range of biomolecules.



Manufactured nanomaterial’s interactions with biomolecules and environmental factors

Nanoparticles, when dispersed in a complex biological milieu adsorb a long lived biomolecular layer containing proteins, lipids and other macromolecules. This complex layer of biomolecules, known as the “protein corona”, will confer the identity of the nanoparticles and be the interface at which they interact with cellular machinery. Therefore, the tapestry of biomolecules presented on the nanoparticle surface will determine not least, the mode of interaction with cellular receptor but potentially, the bio-distribution of nanoparticles in vivo.

In WP5, NanoMILE outlines the nature of how nanoparticles interact with a range of biomolecules that may steer them from their intended target in vivo or impact cellular interactions that may lead to toxicity effects.

In order to evaluate the long lived corona on the surface of nanoparticles, mass spectrometry was performed to develop a list of relevant proteins and lipids that reside on the surface of NanoMILE nanomaterials and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in biologically relevant media such as Human plasma, lung lavage fluid and NanoMILE sera respectively. Mass spectrometry protein analysis showed that when NanoMILE nanomaterials were incubated with human plasma, a series of proteins related to coagulation activation in blood were present on the nanoparticle surface, in particular fibrinogen (Figure 1, mass spectrometry facility at UCD). Fibrinogen interactions with a range of nanomaterials were tested using Fluorescence Correlated Spectroscopy (FCS), a High through-put method to detect local protein concentration adsorbing to the nanoparticle surface. The FCS analysis confirmed that a high fraction of Fibrinogen binds to a range of NanoMILE nanomaterials resulting in high concentrations of fibrinogen surface adsorption and thus, nanoparticle aggregation. Additionally, an experimental nanoparticle-cell interaction model was developed using a Quartz Crystal Microbalance (QCM) to demonstrate that a range of NanoMILE nanoparticles interact with cells surfaces only in the presence of the protein corona (Figure 2).

Predictive modelling analysis was also performed in order to better understand nanoparticle-biomolecule interactions and how they evolve in different conditions, for example pH. When nanoparticles gain access to the cell, they tend to accumulate in acidic compartments called lysosomes. Indeed, the protein corona is carried on the nanoparticle surface to these acidic compartments (demonstrated in WP4). An array of experimental simulations were performed using a known protein Bovine Serum Albumin (BSA) incubated with nanomaterials with a range of different surface charges across a pH range. The simulations demonstrated that at physiological conditions, BSA-nanoparticle interactions are electrostatic; furthermore, at strong pH and when adsorbed to the nanoparticle surface BSA conformation is strongly modified or unfolded (Figure 3).

Fibrinogen and modified, unfolded proteins absorbing to the surface of nanoparticles and becoming a substantial component of the long lived protein corona may lead to unwanted immune detection or bio-accumulation. Fibrinogen has been shown to cross-link neighbouring nanoparticles resulting in aggregation that leads to activation of inflammatory pathways in THP-1 cells (human leukemia monocytes)[1]. Also, modified unfolded proteins have been shown to expose hidden epitopes that are associated with immune detection. Therefore, future studies will include testing ill formed coronas using Fibrinogen and unfolded proteins to understand their interactions with key immune receptors in vitro, using our high throughput QCM model that may lead to a better prediction of the fate of nanoparticles in vivo.

 

 Figure 1: Protein corona analysis using mass spectrometry at UCD

 

 

 

 Figure 2: Attana QCM demonstration of the impact of protein corona on nanoparticle-cell interactions.

 

 

  Figure 3: surface-adsorbed corona proteins can modify or unfold on the surface of nanoparticles depending on pH.

1. Deng, Z.J., et al., Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. Nat Nanotechnol, 2011. 6(1): p. 39-44.

03 May
2016
A High-throughput screening for manufactured nanomaterials
News Photo

NanoMILE establishes a high-throughput screening platform for manufactured nanomaterials.





 

Due to the diversity of manufactured nanomaterials (MNM) regarding chemical composition, surface modification, size, and other parameters the number of materials to be tested for safe application is steadily increasing. For effective safety screening of numerous MNMs it is necessary to speed up the testing by using in vitro test systems and small animals and applying high-throughput/-content (HT/C) methods. High-throughput screening (HTS) is a method of automated testing, allowing a high number of tests simultaneously (e.g. one cell type in a solution with different compounds at different concentrations).

The objectives of NanoMILE in WP4 were to establish a screening platform based on high-throughput techniques (Figure: the platform at the Joint Research Centre (JRC) in Ispra, Italy). By applying these methods, it is expected to uncover adverse outcome pathways and enable efficient and rapid hazard identification and ranking of various MNMs.

The materials selected for this work come from a library of different MNMs all of which had similar size but different chemistry and coatings/modifications and include CeO2, Ag, TiO2, ZnO and SiO2. To date more than 90 MNMs from the NanoMILE library have been screened. To match the experimental conditions, characterisation of the MNMs is performed also in serum containing culture medium under the test conditions. As a positive control, amine-modified polystyrene nanoparticles were used which are already intensively studied by HT (Anguissola et al., 2014). This library was tested in different mammalian cell lines to link physico-chemical properties to multiple adverse effects in different biological systems. Cells cultured in vitro represent ideal high-throughput and ethically acceptable systems to assess toxicity. Yet, simplistic in vitro systems often fail to detect more complex organ-specific toxicity. Therefore, zebrafish embryos are used in addition as a model organism to detect toxicity of MNMs.

The cell lines represent different organs (liver, lung, colon, immune system). The assays used are based on high-throughput/-content (HT/C) techniques. Endpoints such as uptake into cells, cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, steatosis and lysosomal acidification have been studied in cells. The zebrafish embryos were tested for hatching rate, malformations and mortality.

The outcome of the studies is, that the soluble MNMs Ag and ZnO were the most toxic in cells and zebrafish embryos. TiO2 and SiO2 MNMs also triggered toxicity in some but not all cell types and the cell-type specific effects of TiO2 and SiO2 NPs were influenced by the specific coating. CeO2 MNMs were nearly ineffective in our test systems. Overall, the different screening assays come to similar conclusions and complement each other. Therefore, HT/C screening is a versatile method for speedy identification of acutely cyto- and embryo-toxic MNMs. Future HT/C assays need to be established to not only monitor acute cytotoxic effects but to include additional read-outs relevant for e.g. inflammation, genotoxicity and other toxicity pathways.

Reference

Anguissola,S., Garry,D., Salvati,A., O'Brien,P.J., and Dawson,K.A. (2014). High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles. PLoS One 9, e108025.

29 Apr
2016
Aging of Nanoenhanced Textiles: a Comprehensive Sequential Study
News Photo EMPA et al. published in ES&T a Comprehensive Sequential Study on Aging of and release from Nanoenhanced Textiles all along their life cycle.



Unraveling the Complexity in the Aging of Nanoenhanced Textiles: A Comprehensive Sequential Study on the Effects of Sunlight and Washing on Silver Nanoparticles

Denise M. Mitrano, Enzo Lombi, Yadira Arroyo Rojas Dasilva, and Bernd Nowack

 

 

Abstract:

The scientific understanding of nanoparticle (NP) release and transformations they undergo during the product life cycle is hampered by the narrow scope of many research endeavors in terms of both breadth of variables and completeness of analytical characterization. We conducted a comprehensive suite of studies to reveal overarching mechanisms and parameters for nanosilver transformations either still adhered to the fabric or when released after washing. Laboratory prepared nanoenhanced fabrics were investigated: three Ag variants and one Au used as an unreactive reference to separate mechanical from chemical releases. Sequential combinations of sunlight irradiation and/or washing in seven different detergent formulations was followed by NP characterization divided into two groups: (1) dissolved and particulate matter in the wash solutions and (2) the fraction that remained on the fabric. Analytical techniques included spICP-MS, XANES, TEM, SEM, and total metals analysis of fabric digests and wash water filtrates. Sunlight irradiation stabilizes metallic Ag upon washing. Detergents containing oxidizing agents assisted with Ag particle release but not Au NPs, inferring additional chemical mechanisms. While particle size played some role, the NP capping agent/fabric binder combination was a key factor in release. When particles were released, little alteration in size was observed. The use of well-controlled fabrics, unreactive reference materials, and a life-cycle based experimental regime are paramount to understanding changes in Ag speciation and release upon use of nanoenhanced textiles.

06 Apr
2016
Fate and hazard data from NanoFASE and NanoMILE on the same knowledge platform
News Photo A starting point for nucleation of the desperately sought European nanosafety meta-database?



The German big-data and knowledge management company Biomax, who is already operating the NanoMILE KnowledgeBase on hazard characterization of engineered nanomaterials (ENMs), has agreed with the NanoMILE coordinator and NanoFASE partner University of Birmingham, to extend the KnowledgeBase to cover also the additional aspects of relevance to H2020 project NanoFASE on fate characterization of ENMs in the environment.

While initially each project will have its own entry to the portal, and will work with its own set of ENM (although with overlaps as far as scientifically possible), the data are organized in a manner that allows progressively open sharing of the data, for example, as datasets get published. Fate is the key parameter for exposure, and exposure and hazard combined determine the risk. The agreement with Biomax allows the possibility to easily combine hazard and fate data for risk assessment and safety-by-design.