In studying the potential health effects of nanoparticle exposure, scientists rely on cell death as a key indicator. But new research suggests that nanoparticles might require additional safety testing. Brian D. Thrall of Pacific Northwest National Laboratory and his colleagues treated immune cells with iron oxide nanoparticles and showed that although the cells appeared healthy in standard toxicology tests, they struggled to perform one of their key jobs: engulfing pathogenic bacteria (ACS Nano 2013, DOI: 10.1021/nn402145t). The researchers exposed macrophages from mouse bone marrow to superparamagnetic iron oxide nanoparticles. They then added a lipopolysaccharide to the culture, which the macrophages treat as bacteria, and measured the cells’ gene expression with a microarray chip device. The nanoparticles altered the expression of 1,044 genes by at least 50%. The most troubling changes, Thrall says, took place in oxidative stress and inflammation pathways, which play significant roles in macrophages’ ability to detect and clear bacteria. Indeed, when the researchers mixed the macrophages with Streptococcus pneumoniae, macrophages exposed to nanoparticles struggled to take up the pathogen, ingesting just half as much as unexposed cells.