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.
Over the past few years, Quantum Dots have been tested in most biotechnological applications that use fluorescence, including DNA array technology, immunofluorescence assays, cell and animal biology. Quantum Dots tend to be brighter than conventional dyes, because of the compounded effects of extinction coefficients that are an order of magnitude larger than those of most dyes. Their main advantage resides in their resistance to bleaching over long periods of time (minutes to hours), allowing the acquisition of images that are crisp and well contrasted. This increased photostability is especially useful for three-dimensional (3D) optical sectioning, where a major issue is bleaching of fluorophores during acquisition of successive z-sections, which compromises the correct reconstruction of 3D structures. The long-term stability and brightness of Quantum Dots make them ideal candidates also for live animal targeting and imaging. The vast majority of the papers published to date have shown no relevant effects on cells viability at the concentration used for imaging applications; higher concentrations, however, caused some issues on embryonic development. Adverse effects are due to be caused by the release of cadmium, as surface PEGylation of the Quantum Dots reduces these issues. A recently published paper shows evidences of an epigenetic effect of Quantum Dots treatment, with general histones hypoacetylation, and a translocation to the nucleus of p53. In this study, mice treated with Quantum Dots for imaging purposes were analyzed to investigate the impact on protein expression and networking. Differential monoand bidimensional electrophoresis assays were performed, with the individuation of differentially expressed proteins after intravenous injection and imaging analysis; further, as several authors indicate an increase in reactive oxygen species as a possible mean of damage due to the Quantum Dots treatment, we investigated the signalling pathway of APE1/Ref1, a protein involved in the response to oxidative stress. Our results, although preliminary, suggest several interesting point of discussion on Quantum Dots imaging for in vivo diagnostic application, but also for a new therapeutic approach.
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