RESEARCH NEWS
Profiling the cellular response to nanomaterials TOXICOLOGY
With increasing use of nanoparticles in consumer products and medical applications, it is important to understand any potential toxic effects to people and the environment, say researchers from Lawrence Berkeley National Laboratory, the University of California, San Francisco, the University of Kentucky, and DNA chip manufacturer Affymetrix. Other groups have monitored rats, mice, and fish exposed to nanomaterials or measured the toxicity of nanoparticles for different types of cells, but this team investigates the molecular mechanisms responsible for any damage inflicted. Fanqing Frank Chen and colleagues were able to correlate the observed cytotoxicity of two different carbon nanomaterials – multiwalled nanotubes (MWNTs) and multiwalled nano-onions (MWNOs) – with changes in gene expression in human skin fibroblasts and embryonic lung fibroblasts [Ding et al., Nano Lett. (2005), doi: 10.1021/nl051748o]. “We found that multiple pathways are perturbed by exposure to MWNTs and MWNOs, such as immune and inflammatory response, intracellular transportation, stress response, apoptosis, cell-cycle control, and metabolism,” says Chen. The skin and lung cells were exposed to low and high doses of MWNTs and MWNOs. Especially at the higher dose, the nanomaterials induced cell death and reduced proliferation. “Workers that come into contact with large amounts of nanomaterials should protect their skin and lungs from
potential exposure,” the team concludes. They do point out, however, that their study only involved cells. Whole organisms may possess several lines of defense to minimize any toxic effects of nanomaterials. DNA arrays were used to analyze the changes in global gene expression. At low doses, a number of genes were affected that suggests a reduction of cell growth and metabolism. Interestingly, a larger but different set of genes show changes in expression at high doses, impacting cell maintenance, growth, and differentiation. MWNTs place the cells under more stress than MWNOs, inducing innate immune and inflammatory responses that MWNOs do not. This indicates that cells respond to the different structures of the carbon nanomaterials. Some of these genes are also overexpressed in reponse to viral attack, and the researchers note that the nanotubes are a similar size to viruses. The patterns of genes affected also allow the researchers to deduce which biochemical signalling pathways are responsible for the changes in expression. MWNOs downregulate a particular gene that is overexpressed in >25% of breast cancers, a mechanism used by several drugs. “This is the beneficial side of the nanotoxicity story,” says Chen. “We believe that the toxicity of nanomaterials could be used to kill cancer cells.” Jonathan Wood
Magnetic nanoparticles form links NANOPARTICLES Magnetic nanoparticles of controlled size and shape could have potential applications in magnetic recording and medical imaging. Their magnetic properties could also be used to control the formation of nanoparticle assemblies. Chains and rings of such nanoparticles have been assembled as a colloidal solution slowly evaporates on a solid substrate, and two-dimensional assemblies have been created at an air-water interface. Rather than using a surface or interface, physicists at the US National Institute of Standards and Technology have investigated how small magnetic fields might be used to control the assembly of Co nanoparticles in solution [Cheng et al., Langmuir (2005), doi: 10.1021/la0506473]. A 0.05 T field was applied to a colloidal solution of surfactant-coated Co
nanoparticles 15 nm in size. The team, led by Angela Hight Walker, observed centimeter long and micron wide chains aligned along the field direction. The magnetic dipoles of the Co nanoparticles align with the external field, forming linear chains. If the field direction is changed, the chains follow without any indication of individual particles reorienting, showing that the magnetic dipoles are strongly coupled. If the field is removed, the chains become floppy and flex and bend. Transmission electron microscopy shows the chains of nanoparticles are retained but are no longer linear. Where nanoparticles are more concentrated, they take up a hexagonal lattice to minimize the magnetic dipoledipole energy. Gentle agitation results in the chains folding into supercoiled structures. Further agitation fragments
Chains of Co nanoparticles after removing the magnetic field. (© 2005 American Chemical Society.)
the structures, and sonication redisperses the nanoparticles in the solvent. The team characterized the magnetic properties of the nanoparticle assemblies, confirming the interparticle
coupling. At low temperature, the magnetic-field induced assemblies show strong ferromagnetic behavior, with a coercivity that is much greater than random Co nanoparticle assemblies. Jonathan Wood
December 2005
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