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Web Date: February 6, 2014

Researchers Study How Rare-Earth Nanoparticles Trigger Inflammation

Toxicology: Coating the nanoparticles in phosphates could prevent the toxic process
Department: Science & Technology | Collection: Life Sciences
News Channels: Environmental SCENE, Materials SCENE, Nano SCENE
Keywords: rare earth metals, nanoparticle toxicity, toxicology, lung disease
SPINY PARTICLES
Lanthanum oxide nanoparticles sit inert in water (top). But in an acidic phosphate solution, the particles form sea-urchin-like structures as the metal oxide complexes with the phosphates (bottom).
Credit: ACS Nano
Micrographs of lanthanum oxide nanoparticles.
 
SPINY PARTICLES
Lanthanum oxide nanoparticles sit inert in water (top). But in an acidic phosphate solution, the particles form sea-urchin-like structures as the metal oxide complexes with the phosphates (bottom).
Credit: ACS Nano

Rare earth metals—the lanthanides plus scandium and yttrium—are quite popular with materials scientists. The metals are used to make magnets and light-emitting diodes, and metal oxides of the elements are used as catalysts and glass polishes. Because some workers exposed to these materials suffer chronic lung problems, researchers have started to wonder about the toxicity of rare-earth oxide nanoparticles. A new study shows how these nanoparticles damage cells, and then trigger inflammation and lung damage in mice (ACS Nano 2014, DOI: 10.1021/nn406166n). Coating the materials with phosphate could mitigate the risk to workers exposed to the particles, according to the study.

Some workers who mine rare earth metals or use rare-earth polishing agents develop pulmonary fibrosis, the irreversible formation of fibrous connective tissue in the lungs that causes coughing and shortness of breath. It’s not clear how prevalent these problems are, but more and more workers are being exposed to these materials and may be at risk, says Andre Nel, who directs the Center for Environmental Implications of Nanotechnology at the University of California, Los Angeles.

Given those observations, it’s important to understand the risks these materials may pose, and the mechanisms behind them, says Tian Xia, a biophysicist at UCLA who worked with Nel on the new study. In 2012, Xia’s lab was looking at the biological effects of 24 metal oxide nanoparticles. The researchers noticed that the rare earths activated inflammation pathways that have been associated with chronic lung problems. He and Nel decided to do a detailed study of 10 off-the-shelf rare earth oxide nanoparticles, including lanthanum oxide and neodymium oxide, to explore the mechanism behind these materials’ lung toxicity.

They started by looking at what happened to the nanoparticles in acidic brews that resemble the inside of a cell’s lysosome. Previous studies had shown that rare earth nanoparticles are taken up lysosomes within scavenger immune cells in the lungs called macrophages. To mimic this, the researchers added the nanoparticles to acidic solutions containing amino acids and phosphates. Rare earth metal ions dissolved from the surfaces of the nanoparticles and reacted with the phosphates in the solution. The resulting rare-earth-phosphate complexes deposited onto the particles as sea-urchin-like spines.

In macrophage lysosomes, the primary source of phosphate would be the lipids in the lysosome membrane. The researchers put the nanoparticles in an acidic solution inside lipid vesicles that resembled the lysosome membrane. The spine-forming reaction pulled phosphates off the membranes, breaking them open and spilling their contents. Xia thinks that inside macrophages, this stripping causes the lysosomes to break open. Lysosome damage triggers the kinds of inflammatory signalling cascades observed in cells and in animals exposed to rare-earth oxide nanoparticles.

The UCLA team then studied the materials’ effects in mice that had inhaled lanthanum oxide nanoparticles. Macrophages from the lungs of the mice showed evidence of lysosome damage, and these animals developed lung fibrosis. The researchers didn’t see either effect in animals that inhaled titanium dioxide nanoparticles.

Finally, Xia wanted to figure out if the toxic effects could be mitigated. The team placed the rare-earth oxide nanoparticles in a neutral pH solution containing phosphates, leading to a smooth phosphate coating on the particles. In mouse studies, macrophages still took up the coated nanoparticles, but the animals didn’t show signs of lung disease, or signs of the inflammatory cascade that precedes it. Xia says the coating probably wouldn’t hinder the particles’ function, but he acknowledges that’s something that would have to be tested for each application.

Paul Westerhoff, a specialist in sustainable engineering and nanotechnology at Arizona State University, says that this work demonstrates that rare-earth oxides have toxicological properties that are different from other metal oxides. These unique properties mean researchers in academia and industry need to take special care with the materials, he says.

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TOXIC PROCESS
Inside the acidic environment of a cell compartment called the lysosome, rare-earth oxide nanoparticles (large black ball) start to dissolve. The dissolved rare-earth oxides (small black balls) can then bind to the phosphate groups of the lysosome’s membrane (magenta balls). These phosphate-metal complexes (black and magenta) can recombine with the shrunken nanoparticle to form hairy, sea-urchin-like structures (red and black, top right). The process strips the lysosome’s membrane, creating holes that burst open the lysosome (blue arrows, bottom right). These processes trigger inflammation in animals exposed to the nanoparticles.
Credit: ACS Nano
Schematic of how rare-earth oxide nanoparticles interact with lysosome membranes.
 
TOXIC PROCESS
Inside the acidic environment of a cell compartment called the lysosome, rare-earth oxide nanoparticles (large black ball) start to dissolve. The dissolved rare-earth oxides (small black balls) can then bind to the phosphate groups of the lysosome’s membrane (magenta balls). These phosphate-metal complexes (black and magenta) can recombine with the shrunken nanoparticle to form hairy, sea-urchin-like structures (red and black, top right). The process strips the lysosome’s membrane, creating holes that burst open the lysosome (blue arrows, bottom right). These processes trigger inflammation in animals exposed to the nanoparticles.
Credit: ACS Nano
 
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