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

Abstract

While it has been shown that high aspect ratio nanomaterials like carbon nanotubes and TiO2 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 (CeO2) 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 CeO2 nanorods/nanowires were formed along the [211] direction by an “oriented attachment” mechanism, followed by Ostwald ripening. The successful creation of a comprehensive CeO2 nanorod/nanowire combinatorial library allows, for the first time, the systematic study of the effect of aspect ratio on lysosomal damage, cytoxicity 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, CeO2 nanorods induced progressive cytotoxicity and pro-inflammatory effects. 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 long aspect ratio materials.

Toxicity and Protective Effects of Cerium Oxide Nanoparticles (Nanoceria) Depending on Their Preparation Method, Particle Size, Cell Type, and Exposure Route

“…This seems to be in contrast with the fact that nanoceria particles prepared at high temperatures tend to be bigger, more dense, and to have fewer oxygen vacancies and defects. [14] A shape effect was reported by Ji et al, [45] whereby long ceria nanorods (greater than or equal to 200 nm) induced inflammatory responses while short ceria nanorods were nontoxic.…”

Beneficial Effects of Cerium Oxide Nanoparticles in Development of Chondrocyte-Seeded Hydrogel Constructs and Cellular Response to Interleukin Insults

“…73 The aspect ratio of nanoceria is a critical factor in determining its pro-oxidative effects. 29 Nanorods shorter than *200 nm with an aspect ratio of < 16 were found to have little-to-no toxicity, which was attributed to the higher tendency of these nanorods to form bundles. However, their low toxicity may be due to the nanosize-induced increase in the Ce 3 + /Ce 4 + ratio rather than their morphology.…”

“…24 On the contrary, several reports suggest pro-oxidant cytotoxic effects of nanoceria under both in vivo and in vitro conditions. [25][26][27][28][29] The recent work presented in the literature suggests that the synthesis, processing, storage, and handling of nanoceria can have a significant impact on the pro-oxidative and antioxidative properties, and that a comprehensive physicochemical characterization of the nanoparticles is needed. 30 However, nanoceria has not been investigated for either pro-oxidant or antioxidant effects on chondrocytes.…”

Controllable Synthesis and Growth Mechanism of Ceria Nanocubes by Template‐Free Hydrothermal Method

“…Many synthetic methods have been reported, including spray pyrolysis method, [14,15] ultrasound and microwave assisted pyrolysis method, [16] electrochemical method, [17,18] Homogeneous precipitation method [19,20] and so on. Based on these methods, different morphologies of CeO 2 have been fabricated, such as nanorods, [21] nanotubes, [22,23] nanowires, [24,25] microplates, [26] and spherical CeO 2 . [27] Zhang D.S.…”