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 鈥渙riented attachment鈥?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-1尾 production by the human myeloid cell line (THP-1). This
in vitro toxicity study demonstrated that, at lengths 鈮?00 nm and aspect ratios 鈮?2, CeO
2 nanorods induced progressive pro-inflammatory effects and cytotoxicity. The relatively low 鈥渃ritical鈥?length and aspect ratio were associated with small nanorod/nanowire diameters (6鈥?0 nm), which facilitates the formation of stacking bundles due to strong van der Waals and dipole鈥揹ipole 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.
Keywords:
cerium oxide; nanorods; nanowires; aspect ratio; hydrothermal synthesis; oriented attachment; Ostwald ripening; frustrated phagocytosis