Tag Archives: Kenneth Dawson

Environment influences nanomaterial reactions to biological cells

The discussion I’ve seen around nanomaterials and toxicological effects has largely centered on shapes, size, aggregate/agglomerate, etc. By contrast, Carl Walkey’s July 24, 2012 Nanowerk Spotlight essay focuses on nanomaterial surfaces, bare or coated with serum proteins (Note: I have removed links),

Biomolecule adsorption to nanomaterials is usually studied from physiological fluids with suspended biomolecules. Examples include blood serum/plasma, pulmonary surfactant, and synovial fluid. However, until now the amount of those molecules has not been considered relevant to the study. In a recent article appearing in ACS Nano (“Effects of the Presence or Absence of a Protein Corona on Silica Nanoparticle Uptake and Impact on Cells”), Drs. Anna Salvati, Kenneth Dawson, and their colleagues at the University College in Dublin, Ireland, show that if nanoparticles are exposed directly to cells in the absence of suspended biomolecules, the nanoparticles will extract biomolecules directly from cells themselves.

In their experiments, the team exposed silica nanoparticles to cells in two sets. One set was introduced into cell culture media that was supplemented with the usual concentration of fetal bovine serum, and the other into media that had no serum additives. They then incubated both sets of particles with a lung cancer cell line and measured particle uptake kinetics and cell adhesion. Nanoparticles treated under both conditions associated with cells. However, the particles that were incubated in media alone associated to a much greater extent than those that were first incubated in serum. This indicates that the affinity of the bare nanoparticle surface to the cell is much higher than the affinity of an equivalent surface that is coated with serum proteins. [emphasis mine] Similar observations are reported before for other systems, where it was also found that uptake under serum-free conditions is higher.

Moe specifically,

“When the nanomaterial is put in contact with a physiological environment, it is given a menu of possible biomolecules to adsorb” explains Dawson. “It will essentially go shopping for the biomolecules that it wants. Over time, it will exchange with the environment until it finds the things that it really likes most. If you don’t give it enough biomolecules in the form of serum, it will extract components from the cells themselves.”

The same silica nanoparticles exposed to cells in the two different conditions had different cellular responses as well. Most of the serum-coated particles were taken up within vesicles in the cell cytoplasm and produced no overt signs of toxicity. In contrast, the particles without a serum coating adhered to the cell surface to a greater extent, were present in vesicles, and some were also found free-floating in the cytoplasm. Exposure to particles in absence of serum significantly decreased cell viability and caused cells to take on a rounded morphology that is indicative of cell death. Dawson believes that cell death from uncoated particles is the result of strong interactions between the particle surface and the cell surface, which may damage the cell membrane, and/or initiate aberrant signaling cascades. When serum proteins are adsorbed to the nanoparticles, they ‘passivate’ the surface and limit direct nanomaterial-cell interactions.

When considering the early interactions of a nanomaterial with a cell, Dawson points out that one cannot think of the nanomaterial alone. Instead, one must think of the nanoparticle and its adsorbed biomolecules as a fundamental unit. [emphasis mine]

Most importantly,

Dawson believes that researchers must pay closer attention to the composition of the biomolecular environment surrounding the particles and cells when performing in vitro experiments. In other words, it is as important to consider the composition of the biomolecules in the media as it is to consider the chemical nature of the nanoparticle and the cell type. [emphasis mine]

“What’s absolutely clear is that depending on the type of dispersion that you make up, whether you add 10% serum or 20% serum, you get different levels of cell uptake” says Dawson. “Indeed, you get different levels of damage as well. It is therefore not meaningful to say that the nanoparticle is or is not toxic in that simplistic way. You can make a material toxic if you really want to make it toxic. You can make many materials damage cells simply because these have high surface energy. However, in a realistic physiological environment, part of the particle surface is covered and so that kind of damage would not be applicable.”

I encourage anyone who’s interested in nanotoxicology to read Walkey’s essay in full as I’ve excerpted only a portion.

BTW, Carl Walkey is a PhD graduate student at the University of Toronto and a member of the Integrated Nanotechnology & Biomedical Sciences Laboratory (INBS). I last mentioned Walkey in my July 12, 2012 posting about his Nanowerk Spotlight essay on nanotoxicology and animal studies.

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),

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?