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Posted: Dec 08, 2006
Potent antioxidants designed by nanotechnology
(Nanowerk News) There has been a great deal of interest in the toxicity of nanoparticles in the context of respiratory health. The responses of cells exposed to nanoparticles have been studied with regard to toxicity, but very little attention has been paid to the possibility that some types of particles can protect cells from various forms of lethal stress. Research has shown that nanoparticles composed of cerium oxide or yttrium oxide protect nerve cells from oxidative stress and that the neuroprotection is independent of particle size. This has led researchers to the conclusion that there is a potential for engineering this group of nanoparticles for therapeutic purposes.
As one of the researchers, Professor Dave R. Schubert, head of the Cellular Neurobiology Laboratory at Salk, told Nanowerk: "While there has been a great deal of interest in using nanoparticles as drug delivery vehicles, there has been much less interest in exploring the alternative that they can be engineered to have direct beneficial biological effects."
"Our recent study shows that very simple structures can have properties that may have some clinical relevance and opens the possibility of designing nanoparticles that are more potent antioxidants or have more interesting biological properties." says Schubert.
The increasing use of nanotechnology in consumer products, and industrial and medical applications created a great deal of interest in the potential toxicity of nanomaterials. There have, however, been few studies that examine the biological consequences of the exposure of cells or animals to synthetic nanoparticles. Consequently, the molecular and cellular mechanisms for cytotoxicity of various classes of nanoparticles are not yet fully understood.
However, some studies have already shown that for instance some carbon nanospheres and nanotubes behave differently than conventional ultrafine particles, causing fatal inflammation in the lungs of rodents, organ damage in fish and death in ecologically important aquatic organisms and soil-dwelling bacteria.
Schubert and his fellow researcher at Columbia, Professor Siu-Wai Chan, concluded that in contrast to the literature showing that nanoparticles are toxic, nanoparticles composed of cerium and yttrium oxides can have antioxidant properties that promote cell survival under conditions of oxidative stress. The researchers see the potential for engineering this group of nanoparticles for therapeutic purposes.
In their experiments, Schubert and his colleagues showed that cerium and yttrium oxide nanoparticles are able to rescue cells from oxidative stress-induced cell death in a manner that appears to be dependent upon the structure of the particle but independent of its size within the 6–1000 nm range.
There are three alternative explanations for the observation that the cerium oxide and yttrium oxide particles protect from oxidative stress. They may act as a direct antioxidants, they may block ROS production in nerve cells by inhibiting a step in the programmed cell death pathway, or they may directly cause a low level of ROS production that rapidly induces a ROS defense system before the glutamate-induced cell death program is complete. These alternatives were sequentially ruled out.
The researchers concluded that the protective response of the nanoparticles must be dependent upon their physico-chemical properties, relatively independent of their size, and most likely due to their Redox properties.
HRTEM of 2 octahedral CeO2 nanoparticles (Source: Columbia University, Professor Chan)