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Widely used iron nanoparticles exhibit toxic effects on neuronal cells

Researchers at UC San Diego 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," said Sungho Jin, a professor of materials science at UCSD and senior author of a paper to be published in Biomaterials. The paper is currently available on the journal's website. "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."

In their studies, the UCSD researchers used PC12 cells, a line derived from a rat pheochromocytoma. Nerve growth factor prompts PC12 cells to express a variety of neuron-specific genes and generate thin sprout-like cellular extensions called neurites, which are hundreds of times longer than the width of the cell, or up to several millimeters in length. These properties of PC12 cells have made them useful for studying the neurobiological and neurochemical properties of nerve cells.

Jin and the other co-authors of the paper, Thomas R Pisanic, II, Jennifer D. Blackwell, Veronica Shubayev, and Rita Finoes began their laboratory experiments by coating iron oxide nanoparticles with DMSA (dimercaptosuccinic acid), a metal binding agent that polymerizes on the particles' surface. This coating keeps the particles from clumping together in an aqueous solution, and facilitates their engulfment by the PC12 cells via an inward pouching of the cell membrane called endocytosis. What happened next was a surprise.

Jin's group had initially investigated the nanoparticles for use in in vitro studies as a possible way to manipulate nerve cells remotely with magnet
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Contact: Rex Graham
ragraham@ucsd.edu
858-822-3075
University of California - San Diego
28-Mar-2007


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