UCLA

The overarching goal of the work described herein is to elucidate which physicochemical properties contribute to the toxicity of nanoparticles and whether nanoparticles have any special toxicological properties compared to their bulk or micron-sized analogs. We focused specifically on a series of 24 metal oxide nanoparticles (NPs) and on metal (Cu and Ag) NPs and investigated their impacts on enteric bacteria (Escherichia coli and Lactobacillus brevis). For the MOx NPs, we determined that the conduction band energy and hydration energy of the metal correlated most strongly with the toxicity of the nanoparticles in E. coli. Using a series of sub-lethal assays, we demonstrated that the most toxic MOx NPs resulted in ROS generation and membrane damage. For both the Cu and Ag NPs, we compared the magnitude and mechanisms of toxicity to the corresponding metal ions (Cu2+ and Ag+), and in the case of Cu NPs, we also compared the magnitude and mechanisms of toxicity of the NPs to their micron-sized analogs in both E. coli and L. brevis. In the case of the Cu NPs, we found that, although the magnitude of toxicity of the different Cu species correlates with the amount of bioavailable copper, the mechanisms of toxicity for the Cu NPs were significantly different from those of ionic and micron-sized Cu species. In the case of the Ag NP (Ag-BPEI), we performed a genome-wide gene expression analysis in E. coli and compared the results to that of Ag+. This study revealed that the genes up and down regulated by Ag-BPEI are distinct from those affected by Ag+. Taken together, these studies provide important insights both into how to develop new MOx NPs that are safer by design and provide important insights into the unique toxicological properties of some Cu and Ag NPs.