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Nanoparticles toxic to neuronal cells

Recent Ph.D. graduate Thomas R Pisanic, II (left) and materials science professor Sungho Jin.
Recent Ph.D. graduate Thomas R Pisanic, II (left) and materials science professor Sungho Jin.

Researchers at UCSD have discovered that iron-containing nanoparticles being tested for use in several biomedical applications can be toxic to nerve cells and interfere with the formation of their signal-transmitting extensions.

"Iron is an essential nutrient for mammals and most life forms and iron oxide nanoparticles were generally assumed to be safe," says Sungho Jin, a professor of materials science at UCSD and senior author of a paper published in the June issue of Biomaterials. "However, there are recent reports that this type of nanoparticle can be toxic in some cell types, and our discovery of their nano-toxicity in yet another type of cell suggests that these particles may not be as safe as we had once thought."

Nerve growth factor prompts rat cells used in the study to express neuron-specific genes and generate thin sprout-like extensions called neurites, which are up to several millimeters in length.

The cells engulfed specially coated nanoparticles via an inward pouching of the cell membrane called endocytosis. The ingested magnetic particles provide a way to manipulate cells remotely with magnetic force. Eventually the UCSD team had hoped to use nanoparticle-laden nerve cells to bridge regions of damaged neurons. However, when they added nerve growth factor to the cells, some died and many of the survivors exhibited a diminished ability to produce neurites.

When cells were exposed to increasing concentrations of iron oxide nanoparticles, their ability to form threadlike extensions called neurites was impaired.
When cells were exposed to increasing concentrations of iron oxide nanoparticles, their ability to form threadlike extensions called neurites was impaired.

In addition, neurites produced in the presence of iron oxide nanoparticles were less well formed and showed abnormal morphology and neurobiological characteristics.

While studies of iron oxide nanoparticles have focused primarily on their many potential uses, the UCSD researchers said more attention should be paid to their safety. "Our experience leads us to conclude that any analysis of the biocompatibility of nanoparticles should include not just a toxicological study of the component parts," says Thomas R Pisanic, II, a co-author of the paper and a recent Ph.D. graduate, "but also an examination of the total structure as a whole."