Designed Synthesis of CeO2 Nanorods and Nanowires for Studying Toxicological Effects of High Aspect Ratio Nanomaterials

While it has been shown that high aspect ratio nanomaterials like carbon nanotubes and TiO(2) nanowires can induce toxicity by acting as fiber-like substances that damage the lysosome, it is not clear what the critical lengths and aspect ratios are that induce this type of toxicity. To answer this question, we synthesized a series of cerium oxide (CeO(2)) nanorods and nanowires with precisely controlled lengths and aspect ratios. Both phosphate and chloride ions were shown to play critical roles in obtaining these high aspect ratio nanostructures. High-resolution TEM analysis shows that single-crystalline CeO(2) nanorods/nanowires were formed along the [211] direction by an "oriented attachment" mechanism, followed by Ostwald ripening. The successful creation of a comprehensive CeO(2) nanorod/nanowire combinatorial library allows, for the first time, the systematic study of the effect of aspect ratio on lysosomal damage, cytotoxicity, and IL-1β production by the human myeloid cell line (THP-1). This in vitro toxicity study demonstrated that, at lengths ≥200 nm and aspect ratios ≥22, CeO(2) nanorods induced progressive pro-inflammatory effects and cytotoxicity. The relatively low "critical" length and aspect ratio were associated with small nanorod/nanowire diameters (6-10 nm), which facilitates the formation of stacking bundles due to strong van der Waals and dipole-dipole attractions. Our results suggest that both length and diameter components of aspect ratio should be considered when addressing the cytotoxic effects of high aspect ratio materials.