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Details of Grant 

EPSRC Reference: EP/H045031/1
Title: The radical nature of oxidative stress triggered by metal nanoparticles
Principal Investigator: Chechik, Professor V
Other Investigators:
Genever, Professor P
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of York
Scheme: Standard Research
Starts: 01 September 2010 Ends: 15 January 2014 Value (£): 357,959
EPSRC Research Topic Classifications:
Analytical Science Chemical Biology
Chemical Structure Physical Organic Chemistry
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
24 Feb 2010 Physical Sciences Panel - Chemistry Announced
Summary on Grant Application Form
Nanomaterials have unique chemical and physical properties and therefore have many exciting applications. However, the impact of nanomaterials on human health and environment is poorly understood. In order to enable future development of nanotechnology, basic understanding of how nanomaterials interact with cells is urgently needed.Some studies found that toxic effects of nanoparticles in cells are usually dominated by oxidative stress, e.g., generation of reactive oxygen species. Two possible explanations can be used to account for this phenomenon. Firstly, oxidative stress could be caused by the natural reaction of the cell to the nanoparticle exposure, triggered by the stimulation of receptors by the nanoparticles or disruption of normal biochemical mechanisms. Secondly, reactive oxygen species could be generated directly by reaction of cell constituents with the nanoparticles. The relative role of these two factors is not currently understood.In a recent project, we found that some metal nanoparticles are capable of generating free radicals upon reaction with oxygen and organic compounds. This is not surprising as the high surface energy of nanoparticles is expected to result in high chemical reactivity. Inspired by these results, we propose that the oxidative stress triggered by metal nanoparticles in cells may be related to their reactivity, e.g., their ability to generate free radicals upon reaction with oxygen and organic compounds. This project is aimed at establishing such structure-reactivity-toxicity relationship. We will investigate the properties of a broad range of nanoparticles in biological and non-biological environments. The nanoparticle-initiated free radical flux in organic and aqueous systems will be compared to oxidative stress in cells. Formation of radicals will be detected using EPR spectroscopy. A significant advantage of this method is that it can be applied to biological as well as non-biological systems. Additionally, it provides structural and quantitative information on the free radicals formed. We will also determine which cell constituents are most reactive with nanoparticles, in order to unravel the main routes of nanoparticle toxicity and link this toxicity to the particle structure, morphology and chemical composition. We believe that this study will not only provide comparative information of nanoparticle toxicity, but will also lead to a deeper understanding of what properties of nanoparticles are responsible for causing oxidative stress. Such molecular understanding-based knowledge is essential for predicting toxicity of new materials and finding ways for reducing undesired effects on health and environment. We believe that in the long term, such mechanistic studies will help to ensure safety of the future applications of nanomaterials.
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Organisation Website: http://www.york.ac.uk