Nanoparticles Explored for Preventing Cell Damage

Engineers investigate using nanoparticles both as a preventative and a treatment for disease.

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By Cecile Gonzalez, National Science Foundation

Sudipta Seal is enthralled by nanoparticles, particularly those of a rare earth metal called cerium. The particles are showing potential for a wide range of applications, from medicine to energy.

Seal is a professor of materials science and engineering at the University of Central Florida (UCF), and several years ago, he and his colleagues engineered nanoparticles of cerium oxide (CeO2), a material long used in ceramics, catalysts, and fuel cells. The novel nanocrystalline form is non-toxic and biocompatible--ideal for medical applications.

Since then, the researchers found that cerium oxide nanoparticles have two additional medical benefits: they behave like an antioxidant, protecting cells from oxidative stress, and they can be fine-tuned to potentially deliver medical treatments directly into cells.

Oxidative Stress = Major Headache

Oxidative stress has been implicated as a cause of arthritis, heart disease, and even aging. It also plays a role in several incurable blinding diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal degeneration.

Oxidative stress occurs when too many reactive oxygen species (ROS) are present. These powerful molecules are generated by exposure to ionizing radiation and by commonplace reduction--oxidation reactions within cells. (Peroxide and free radicals are two examples of ROS.)

Usually, enzymes known as antioxidants protect cells from oxidative stress by disarming ROS and minimizing their toxic effects. But sometimes, the number of ROS overwhelms a biological system, causing damage to proteins, DNA, and other cellular materials.

Engineering Nanoparticles With Antioxidant Powers

Seal and his colleagues--James McGinnis, a vision scientist at the University of Oklahoma Health Sciences Center, Artem Masunov, a theoretical chemist at UCF, and William Self, a molecular and micro-biologist at UCF--engineered special cerium oxide nanoparticles, which they call nanoceria, for tailored biomedical applications.

In a nanocrystalline form, cerium oxide is a powerful antioxidant because its latticework crystal structure has many vacancies that can capture oxygen, and the material has a large surface area. Self showed that nanoceria mimic the activity of superoxide dismutases (SOD), an antioxidant that can stop the deadly chain reactions caused by ROS.

Nanoceria are also able to regenerate their antioxidant abilities. "Due to this catalytic property," explains Seal, "repeated dosing with nanoceria may not be needed, as it is with certain antioxidant vitamins."

In a biological paradox, ROS are actually required for some beneficial cellular reactions. Fortunately, nanoceria do not deactivate all ROS. Rather, says Seal, "they reduce the amount of ROS to a certain low level, thus striking a perfect balance."

Stopping Eye Damage

Because they are bombarded by light and have a very high rate of oxygen metabolism, cells in the retina encounter relatively high numbers of ROS. Seal and his colleagues hypothesized that ROS may represent an "Achilles' heel" of blinding diseases, which can be specifically targeted using cerium oxide nanoparticles.

To test their hypothesis, the researchers used mice whose eyes have retinal defects similar to those found in patients with age-related macular degeneration. They treated some of the mice with nanoceria and then compared the number of lesions that occurred in their retinas. The researchers' results, published in Nature Nanotechnology, indicate that the nanoceria prevented about 85 percent of the damage to the retina.

Through a newly launched company, McGinnis is pursuing the development of nanoceria medical treatments for several causes of vision loss: the genetic eye disease retinitis pigmentosa (RP), age-related macular degeneration, and diabetic retinopathy.

Special Delivery

Seal--and colleagues Masunov, Self, Sanku Mallik of North Dakota State University, and Christopher Reilly of Virginia Tech --are also investigating the use of cerium oxide in drug delivery.