Nanosafety Research Research Articles

Oxidative potential of silver nanoparticles measured by electron paramagnetic resonance spectroscopy

The oxidative potential (OP) of engineered nanomaterials (NM) is considered as promising metric for nanosafety research and risk assessment. Here, we present findings on the analysis of the oxidative potential of three different silver NM by means of a complementary electron paramagnetic resonance (EPR) spectroscopy-based approach, i.e., using the spin trap DMPO (5,5-dimethyl-1-pyrroline-N-oxide) and the spin probe CPH (l-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride). The results revealed that both methods are principally applicable for OP analysis of nanosilver. However, one of the Ag NM (i.e., NM300) did not cause notable OH▪ generation in the presence of hydrogen peroxide, while a clear OP was detected using the CPH method for all three Ag NPs tested. For the NM300, also a strong OH▪ scavenging potency could be demonstrated, which was due to its surfactant-containing dispersant. This finding may explain for the reported differences in effects of this widely applied reference nanosilver versus other types of Ag NM in toxicological studies. Our findings also demonstrate the relevance of using more than one assay to determine the OP of NM in general.

Nanomaterials hoax scientists: Nanosafety research on the right track?

Nanomaterials hoax scientists: Nanosafety research on the right track?

Responsible Research Is Not Good Science: Divergences Inhibiting the Enactment of RRI in Nanosafety

The desire to guide research and innovation in more ‘responsible’ directions is increasingly emphasised in national and international policies, the funding of inter- and trans-disciplinary collaborations and academic scholarship on science policy and technology governance. Much of this growth has occurred simultaneously with the development of nanoscale sciences and technologies, where emphasis on the need for responsible research and innovation (RRI) has been particularly widespread. This paper describes an empirical study exploring the potential for RRI within nanosafety research in Norway and Denmark. It identifies three different ways nanosafety scientists relate to core RRI criteria, demonstrating areas of both convergence and divergence between their views and those of academics and policymakers currently defining and working to promote RRI. The paper identifies a range of practical barriers and cultural differences that are creating such divergences and inhibiting the enactment of RRI within the particular site of research laboratories. It concludes that the identified differences and challenges demand critical reflection on both the appropriateness and applicability of RRI characteristics for enactment at the level of individual research scientists. Significant changes are therefore advocated as required if RRI, as currently imagined and promoted, is to become an integral mode of scientific culture.

Reliability for Nanosafety Research – Considerations on the Basis of a Comprehensive Literature Review

AbstractAfter 15 years of intense research on the risks of nanomaterials, the evaluation of specific nanomaterials is still difficult. The more research is performed, the more studies which demonstrate critical effects of nanomaterials are published. In this regard, it should be noted that most published studies do not show usable toxicological results, although these are well‐cited as such and appear as headlines in the daily press. There is a lack of reliability of the scientific data, especially for nanosafety research. Here, this statement is illustrated by examples and solutions are shown.

Nano-safety Research: Examining the Associations among the Biological Effects of Nanoparticles and Their Physicochemical Properties and Kinetics.

In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now an important part of our daily lives. Despite our increasing exposure to nanoparticles, however, information regarding the absorption, distribution, metabolism, excretion, and toxicity of nanoparticles remains limited. In this review, we introduce our group's ongoing research into the biological effects and toxicities of nanoparticles, which we broadly refer to as "nano-safety research." In addition to determining the biological effects of nanoparticles and elucidating the underlying mechanisms of those effects, we are also exploring the associations among the physicochemical properties and kinetics of nanoparticles. Furthermore, we are currently developing a battery of biomarkers that we hope will be used to predict the biological effects of nanoparticles during the early stages of development. Our research provides valuable basic information on the safety of nanoparticles. We hope that this information will be used for the development of better assessments of nanoparticles safety and for the creation of more appropriate regulations to ensure not only the safety but also the sustainability of nanotechnology.

Systems biology approaches in nanosafety research with special reference to carbon-based nanomaterials

Systems biology approaches in nanosafety research with special reference to carbon-based nanomaterials

Quantitative uptake of colloidal particles by cell cultures

The use of nanotechnologies involving nano- and microparticles has increased tremendously in the recent past. There are various beneficial characteristics that make particles attractive for a wide range of technologies. However, colloidal particles on the other hand can potentially be harmful for humans and environment. Today, complete understanding of the interaction of colloidal particles with biological systems still remains a challenge. Indeed, their uptake, effects, and final cell cycle including their life span fate and degradation in biological systems are not fully understood. This is mainly due to the complexity of multiple parameters which need to be taken in consideration to perform the nanosafety research. Therefore, we will provide an overview of the common denominators and ideas to achieve universal metrics to assess their safety. The review discusses aspects including how biological media could change the physicochemical properties of colloids, how colloids are endocytosed by cells, how to distinguish between internalized versus membrane-attached colloids, possible correlation of cellular uptake of colloids with their physicochemical properties, and how the colloidal stability of colloids may vary upon cell internalization. In conclusion three main statements are given. First, in typically exposure scenarios only part of the colloids associated with cells are internalized while a significant part remain outside cells attached to their membrane. For quantitative uptake studies false positive counts in the form of only adherent but not internalized colloids have to be avoided. pH sensitive fluorophores attached to the colloids, which can discriminate between acidic endosomal/lysosomal and neutral extracellular environment around colloids offer a possible solution. Second, the metrics selected for uptake studies is of utmost importance. Counting the internalized colloids by number or by volume may lead to significantly different results. Third, colloids may change their physicochemical properties along their life cycle, and appropriate characterization is required during the different stages.

Nanoparticle dosage-a nontrivial task of utmost importance for quantitative nanosafety research.

For a detailed and correct understanding of effects of colloidal nanoparticles exposed to organisms, a correlation of such effects to the physicochemical properties of the nanoparticles is a necessity. Such correlation is complex by the fact that many physicochemical parameters such as size, shape, surface charge, and colloidal stability are interlinked, and nontrivial to experimentally determine. This review aims to give an overview regarding such correlations. Particular focus will be given on the role of determining nanoparticle concentrations, which is the basis for most quantitative toxicity evaluations. A comparison of mass versus particle number concentrations is given, and their respective differences are highlighted. WIREs Nanomed Nanobiotechnol 2016, 8:479-492. doi: 10.1002/wnan.1378 For further resources related to this article, please visit the WIREs website.

Systems Biology in Nanosafety Research

In his famous essay, Lazebnik [1] discussed whether a biologist can fix a broken radio and suggested that applying the ‘biologist approach’ to a broken radio will likely not lead to a successful end, while any engineer or even a trained repairman evidently could fix the radio. In biology, the study of molecules one by one is fine for gathering information on how molecules work, but deciphering biological mechanisms, or the function of biological systems, is a different story. One difference between an engineer and a biologist, according to Lazebnik, lies in the language: in biology, language is oftentimes vague and nonquantitative which limits the possibility of making predictions [1]. In systems biology, a quantitative and predictive language is adopted to describe biological knowledge in order to understand how molecules act together within the network of interactions that makes up a living system. Systems biology, in other words, is the holistic analysis of complex systems. Indeed, systems biology can be defined as the computational and mathematical modeling of complex biological systems, in contrast to the traditional, reductionist approach to biology. Common technology platforms that are deployed to obtain complex datasets are transcriptomics, proteomics, metabolomics and epigenomics. However, systems biology should not be seen merely as the generation of lists of genes, proteins or metabolites using such omics platforms; the objective is to exploit these data and to develop quantitative models that describe the biological system and its response to individual perturbations (see [2] for an excellent introduction to this subject). Furthermore, systems biology can be seen as an iterative interplay between discoveryand hypothesis-driven science: “global observations (discoveries) are matched against model predictions (hypotheses) in an iterative manner, leading to the formation of new models, new predictions, and new experiments to test them” [2]. Systems toxicology, in turn, has been described as “the integration of classical toxicology with quantitative analysis of large networks of molecular and functional changes occurring across multiple levels of biological organization”, and it has been suggested that its application could be part of a new and improved risk assessment [3]. This is nothing less than a paradigm shift in the way that toxicology is conducted. Importantly, systems toxicology – and systems biology in general – relies heavily on computational approaches to manage, analyze and interpret the data generated by large-scale experiments, and computer databases are thus an integral feature of this approach [2]. To this end, commonly accepted repositories and software environments are crucially important [4]. This does not mean that the introduction of systems toxicology approaches is breaking the rice bowl of the classically trained toxicologist. Instead, the ‘new’ toxicology is Systems biology in nanosafety research

ChemInform Abstract: Nanosafety Research — Are We on the Right Track?

AbstractReview: 84 refs.

Nanosafety research--are we on the right track?

The number of studies that have been published on the topic of nanosafety speaks for itself. We have seen an almost exponential rise over the past 15 years or so in the number of articles on nanotoxicology. Although only a couple of hundred papers had appeared on the topic of "Nanomaterials: environmental and health effects" before 2000, this number has exploded to over 10 000 since 2001. Most of these studies, however, do not offer any kind of clear statement on the safety of nanomaterials. On the contrary, most of them are either self-contradictory or arrive at completely erroneous conclusions. Three years ago in this Journal we underscored the deficiencies in the way these studies were designed and pointed out the sources of error in the methods used. Now, on the basis of a comprehensive review of the literature and with the help of selected toxicological end points, we attempt to indicate where the significant weaknesses of these studies lie and what we must improve in the future.

Cover Picture: Are We Entering the Nano Era? (Angew. Chem. Int. Ed. 46/2014)

Nanotechnology has become ubiquitous in our everyday lives, from medicine and information storage to sunscreens and cosmetics. With so many applications, its risks also need to be considered. This issue, which starts with an Editorial by Y. Xia on page 12268, gives an overview of the most recent developments and challenges of nanotechnology. It contains five Reviews on current topics including nanosafety research, nanoparticles in the environment, inorganic nanoparticles, soot nanoparticles, and nanoparticles for drug delivery, as well as Communications that cover the whole spectrum of nanotechnology, from fundamental studies to catalysis, energy, and materials research. Nanotechnology has become ubiquitous in our everyday lives, from medicine and information storage to sunscreens and cosmetics. With so many applications, its risks also need to be considered. This issue, which starts with an Editorial by Y. Xia on page 12268, gives an overview of the most recent developments and challenges of nanotechnology. It contains five Reviews on current topics including nanosafety research, nanoparticles in the environment, inorganic nanoparticles, soot nanoparticles, and nanoparticles for drug delivery, as well as Communications that cover the whole spectrum of nanotechnology, from fundamental studies to catalysis, energy, and materials research. Nanoshells F. Caruso, Y. Lee, I. S. Choi, and co-workers show in their Communication on page 12420 that a cytoprotective nanoshell can be formed on individual yeast cells from a coordination complex of tannic acid and FeIII ions.1 Binary Superlattices In their Communication on page 12548 ff., S.-M. Choi et al. report highly ordered binary superlattices of 1D nano-objects obtained from single-walled carbon nanotubes and cylindrical surfactant micelles.1 DNA Nanotechnology S. Howorka et al. report in their Communication on page 12466 ff. how nanopores composed of folded DNA featuring a hydrophobic belt of ethyl phosphorothioate groups insert into bilayer membranes and kill cancer cells.1

Bibliometrics Analysis of Nanosafety Research

Bibliometric methods was used to outline the scientific research of nanosafety around the word. Categories of nanosafety, publications trend, geographical distribution, authors, and journals were chosen as the basic parameters in this study. In a depth, key terms and classical papers in nanosafety were also analyzed. The results shown that the research area of nanosafety topic are mainly in science technology, chemistry and materials science, the categories of nanosafety in Web of Science are in nanoscience nanotechnology, chemistry multidisciplinary and materials science multidisciplinary. Publications of nanosafety have approximate linear trends from 2003 to 2013. The countries with most publications have been USA, Germany, China and the UK. Chinese Academic Science and Osaka University are high productive institutions in nanosafety research. Additional, Journal of Nanoparticle Research, Yakugaku Zasshi-Journal of the Pharmaceutical Society of Japan and Risk Analysis were the most representative journals in the field of nanosafety topic. Co-words analysis of nanosafety shown that nanosafety are most aim to nanoparticles. Classical papers of nanosafety were mainly during 2006 to 2010 have been cited time more than 90 times and the Web of Science shows that these papers had important effect on nanosafety progress.

Phagocytosis of nano-sized titanium dioxide triggers changes in protein acetylation

Nano-sized titanium dioxide (nTiO2) is one of the most produced engineered nanomaterials and therefore carries a high risk for workplace exposure. In several nanosafety studies, exposure to nTiO2 has been shown to trigger inflammation in mice lung and to cause oxidative stress. Here, cytoplasmic proteome changes in human monocyte derived macrophages were investigated with two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry to evaluate the adverse cellular effects after exposure to different types of TiO2 nanoparticles (NPs). Both studied TiO2 NPs (rutile TiO2 with or without silica coating) evoked similar proteome alterations. The identified proteins were linked to metabolic homeostasis, cytoskeleton remodeling and oxidative stress. The abundances of chloride intracellular channel protein 1 and cathepsin D changed only after exposure to nTiO2 as compared to a coarse particle analog. Enrichment analysis revealed that 70% of the proteins with changed intensities contained known acetylation sites, and it was possible to confirm a significant induction of cytoplasmic protein acetylation after nTiO2 exposure. The course of the events during phagocytosis could account for the observed membrane maintenance, metabolic and cytoskeletal protein expression changes. Lysine acetylation of cytoplasmic proteins in macrophages is emerging as a major cell regulation mechanism after nTiO2 exposure. While the amount of nanosafety research conducted in recent years has been constantly increasing, proteomics has not yet been utilized widely in this field. In addition, reversible protein post-translational modifications (PTMs) such as acetylation and phosphorylation have not been investigated in-depth in nanomaterial exposed cells. Proteome changes observed in nanomaterial exposed macrophages revealed active phagocytosis of the particles and provided new insights into underlying mechanisms of biological responses to nTiO2 exposures. Moreover, reversible protein acetylation might be a major cellular regulation event occurring in nanomaterial exposed cells.

ITS-NANO - Prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy

BackgroundTo assess the risk of all nanomaterials (NMs) on a case-by-case basis is challenging in terms of financial, ethical and time resources. Instead a more intelligent approach to knowledge gain and risk assessment is required.MethodsA framework of future research priorities was developed from the accorded opinion of experts covering all major stake holder groups (government, industry, academia, funders and NGOs). It recognises and stresses the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling approaches as key components of the current and future risk assessment of NMs.ResultsThe framework for future research has been developed from the opinions of over 80 stakeholders, that describes the research priorities for effective development of an intelligent testing strategy (ITS) to allow risk evaluation of NMs. In this context, an ITS is a process that allows the risks of NMs to be assessed accurately, effectively and efficiently, thereby reducing the need to test NMs on a case-by-case basis.For each of the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling, key-priority research areas are described via a series of stepping stones, or hexagon diagrams structured into a time perspective. Importantly, this framework is flexible, allowing individual stakeholders to identify where their own activities and expertise are positioned within the prioritisation pathway and furthermore to identify how they can effectively contribute and structure their work accordingly. In other words, the prioritisation hexagon diagrams provide a tool that individual stakeholders can adapt to meet their own particular needs and to deliver an ITS for NMs risk assessment. Such an approach would, over time, reduce the need for testing by increasing the reliability and sophistication of in silico approaches.The manuscript includes an appraisal of how this framework relates to the current risk assessment approaches and how future risk assessment could adapt to accommodate these new approaches. A full report is available in electronic format (pdf) at http://www.nano.hw.ac.uk/research-projects/itsnano.html.ConclusionITS-NANO has delivered a detailed, stakeholder driven and flexible research prioritisation (or strategy) tool, which identifies specific research needs, suggests connections between areas, and frames this in a time-perspective.

Building expert consensus on problems of uncertainty and complexity in nanomaterial safety

A modified Delphi Method was used to determine the opinions of a range of experts from academia, industry and government in the field of nanotechnology, mainly those working in the areas of safety, occupational and environmental health, and nanotoxicology. The focus was on uncertainty and complexity. A questionnaire was prepared and the responses were collated and arranged by theme in a draft text. This text was then used in a second iteration for further comments both in a live plenary discussion at a nano-safety conference in Prague (November 2010) and subsequently electronically. A draft was prepared for final comments from a small panel before completion of the report. The participants identified the following ten priorities in the development of nano-safety: the need for realistic exposure scenarios, better established dose–response relationships, improved extrapolation from in vitro to in vivo, identification of the most relevant assessment parameters, understanding the dynamic biological interfaces, long term studies, information about stability and reactivity, understanding the behaviour of the protein corona, having test guidelines adapted to manufactured nanomaterials, and the development of more advanced statistical and computational methods. The discussions also investigated the basic nature of the uncertainties and how to distinguish between mere lack of data and intrinsic uncertainties that are a consequence of the complexity of living systems. The results of the consensual process are presented here, together with the identified priorities and some implications for strategy in nano-safety research and development.