Nanopartículas de Hierro Ampliamente Usadas Exhiben Efectos Tóxicos en Células NeuronalesContributed by: Anonymous · Views: 1,323
Contributed by: Anonymous · March 29, 2007 @ 01:00 PM MDT · Views: 1,323
Widely Used Iron Nanoparticles Exhibit Toxic Effects on Neuronal CellsMarch 28, 2007
By Rex Graham
These PC12 cells were exposed to no (left), low (center), or high (right) concentrations
of iron oxide nanoparticles in the presence of nerve growth factor, which normally stimulates
these neuronal cells to form thread-like extensions called neurites
“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 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.”
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.
Recent UC San Diego Ph.D. graduate Thomas R Pisanic, II (left) and materials science professor Sungho Jin
Jin’s group had initially investigated the nanoparticles for use in in vitro studies as a possible way to manipulate nerve cells remotely with magnetic force. Eventually they had hoped to conduct in vivo experiments, using nanoparticles-laden nerve cells to bridge regions of damaged neurons. However, when they added nerve growth factor to nanoparticle-laden cells in culture flasks, they observed toxic dose-dependent effects: some cells died, and many of the survivors exhibited a diminished ability to produce neurites.
In their experiments, PC12 cells that had not been exposed to magnetic nanoparticles generated three neurites in response to nerve growth factor. However, exposure to a low concentration of iron oxide nanoparticles resulted in the production of fewer than three neurites per cell in response to growth factor addition. A 10-fold increase in the concentration of nanoparticles led to the production of two neurites per cell, and a 10-fold increase of that concentration resulted in only one neurite per cell. Additionally, neurites produced in response to the growth factor in the presence of iron oxide nanoparticles were less well formed and also showed abnormal morphology and neurobiological characteristics.
The researchers also studied long protein polymers inside the PC12 cells that make up the cytoskeletal structure. They found that iron oxide nanoparticles resulted in fewer and less organized microtubules and microfilaments, protein polymers involved in cell motility and cell shape.
“It’s worth noting that neither iron oxide nanoparticles alone, nor the coating material alone are overtly toxic, but combining the two to create water-soluble nanoparticles has a completely different effect,” said Pisanic, who carried out the studies as a part of a Ph.D. thesis project at UCSD.
Iron oxide nanoparticles
Many researchers throughout the world are also studying the use of iron-containing nanoparticles in gene therapy, magnetic resonance imaging (MRI), and other medically important applications. While studies have focused primarily on the many potential uses of nanoparticles, Jin 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,” said Pisanic, “but also an examination of the total structure as a whole.”
University of California, San Diego