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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 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-1? 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.

SUBMITTER: Ji Z

PROVIDER: S-EPMC3651271 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Designed synthesis of CeO2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials.

Ji Zhaoxia Z Wang Xiang X Zhang Haiyuan H Lin Sijie S Meng Huan H Sun Bingbing B George Saji S Xia Tian T Nel André E AE Zink Jeffrey I JI

ACS nano 20120607 6

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 ...[more]

PMID: 22564147

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Project description:BackgroundThe most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures.ResultsCarbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm2) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers.ConclusionsInduction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.

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Designed synthesis of CeO2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials.

Publications

Designed synthesis of CeO2 nanorods and nanowires for studying toxicological effects of high aspect ratio nanomaterials.

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