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Size really does matter: nanoform polyphenols show reversed antioxidant effects

6 September 12

Natural chemicals found in tea are known to have potential for the treatment and prevention of a number of human cancers, but their effects can be altered when they are used in their nanoparticle form, warn researchers from the University of Bradford.

A study, published online on 4 September 2012 in Nanomedicine, compared the properties of polyphenols in different forms on white blood cells taken from patients with colorectal cancer and from healthy volunteers. It found that the known antioxidant properties of these substances can be reversed when they are used in their nanoparticle form. Antioxidants prevent damage to DNA and other molecules which can be caused by free radicals.

Led by Professor Diana Anderson from Bradford's School of Life Sciences, the research compared the antioxidant responses of two polyphenols, called ECGC and theaflavins. These were provided by Dr Gupta, Director of the Indian Institute of Toxicology Research (IITR). The findings showed that when used in bulk form, these polyphenols exhibited their anticipated antioxidant responses, but the nanoform at higher concentrations had the reverse effect and exhibited statistically significant pro-oxidant effects, which can cause increased DNA damage.

"We didn't expect these changes," says Professor Anderson. "When my PhD student came to me with the results, she assumed she'd made a mistake. But it struck me that I'd seen this happen before - in a study we published in 1994 describing a dose-related switch of properties in Vitamin C in the presence of hydrogen peroxide. At the time I didn't think much about it, but this is the first time I've seen this happen with the nanoform of a compound."

During the research, lymphocytes (a type of white blood cell) were treated with the platinum-based chemotherapeutic drugs, oxaliplatin and satraplatin. These drugs bind to DNA efficiently, forming a variety of links that block replication and transcription, and affect signalling pathways which trigger death in cancer cells. At the same time, the lymphocytes were treated with the polyphenols, both in their bulk forms and their nanoforms. The relative modifications in DNA damage caused by the different forms and concentrations of the polyphenols was measured by Comet assay tests.

"It's not clear why this switch happens," says Professor Anderson. "It may be dependent on the compound and on the type of cancer under investigation. And of course in vivo research may show different results again. But it's certainly of interest that these natural polyphenol antioxidants may not always behave as chemopreventives. Nanotechnology has preceded nanotoxicology by a number of years and we nanotoxicologists are having to catch up."

The study may have implications for the development of new drugs based on nanotechnology. The antioxidant properties of tea polyphenols are well documented, and there is a great deal of research being undertaken to harness these properties and apply them in new medicines. However, studies such as this show that whilst nanotechnology has shown enormous benefit in many areas of science, its application in medicine may not be simple.

"Using nanoforms of chemicals is increasingly being looked at in an effort to boost the efficacy of drugs, but this study shows that the nanoform doesn't always produce a more effective response. In this case, it suggests that the bulk form of tea polyphenols is more useful as a chemopreventive."

The study wass published on 4 September in Nanomedicine and was funded by United Kingdom Indian Education Research Initiative grant jointly awarded to Professors Alok Dhawan of IITR and Diana Anderson, University of Bradford.

6 September 12

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