Crystal structure mediates mode of cell death in TiO2 nanotoxicity
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Certain properties that nanoparticles possess differentiate them from their bulk counterparts, and these characteristics must be evaluated prior to nanoparticle studies and include: size, shape, dispersion, physical and chemical properties, surface area, and surface chemistry. Early nanotoxicity studies evaluating TiO2 have yielded conflicting data which identify either size or crystal structure as the mediating property for nano-TiO2 toxicity. However, it is important to note that none of these studies examined size with the crystal structure composition controlled for or examined crystal structure while controlling the nanoparticle size. The goal of this study was to evaluate the role of size and crystal structure in TiO2 nanotoxicity while controlling for as many other nanoproperties as possible using the HEL-30 mouse keratinocyte cell line as a model for dermal exposure. In the size-dependent studies, all the nanoparticles are 100% anatase, and aggregate sizes were determined in order to take into account the effect of agglomeration on size-dependent toxicity. In addition, varying crystal structures were assessed while the size of the nanoparticles was controlled. We were able to identify that both size and crystal structure contribute to cytotoxicity and that the mechanism of cell death varies based on crystal structure. The 100% anatase TiO2 nanoparticles, regardless of size, induced cell necrosis, while the rutile TiO2 nanoparticles initiated apoptosis through formation of reactive oxygen species (ROS).
KeywordsNanotoxicity Nano-size Crystallinity Keratinocytes Nanotechnology Health effects EHS
The authors would like to thank Col J. Riddle for his strong support and encouragement for this research. They would also like to thank Dr. Amanda Schrand, Mr. Michael Moulton and Ms. Katherine Szczublewski for their technical assistance. Dr. Braydich-Stolle is funded by a Post-Doctoral Fellowship through the National Research Council. Ms. Nicole Schaeublin is supported by the Biosciences and Protection Division, Human Effectiveness Directorate, Air Force Research Laboratory through the Henry Jackson Foundation. Mr. Richard Murdock is funded by the Biosciences and Protection Division, Human Effectiveness Directorate, Air Force Research Laboratory under the Oak Ridge Institute for Science and Education. This work was supported by the Air Force Office of Scientific Research (AFOSR) Project (JON # 2312A214). Dr. Pratim Biswas and Mr. Jingkun Jiang acknowledge support from the U.S. Department of Defense (AFOSR) MURI Grant (FA9550-04-1-0430).
- Braydich-Stolle LK, Lucas B, Schrand A, Murdock RC, Lee T, Schlager J, Hussain SM, Hofmann MC (2008) Silver nanoparticles disrupt GDNF signaling in spermatogonial stem cells independent of nanoparticle size and coating (submitted)Google Scholar
- Bucher J, Masten S, Moudgil B, Powers K, Roberts S, Walker N (2004) Developing experimental approaches for the evaluation of toxicological interactions of nanoscale materials. Final workshop report, 3–4 November 2004, University of Florida, Gainesville, FL, pp 1–37Google Scholar
- Dharmarajan AM, Hisheh S, Singh B, Parkinson S, Tilly KI, Tilly JL (1999) Antioxidants mimic the ability of chorionic gonadotropin to suppress apoptosis in the rabbit corpus luteum in vitro: a novel role for superoxide dismutase in regulating bax expression. Endocrinology 140:2555–2561. doi: 10.1210/en.140.6.2555 PubMedCrossRefGoogle Scholar
- Ellsworth DK, Verhurst D, Spitler TM, Sabacky BJ (2000) Titanium nanoparticles move to the marketplace. Chem Innov 30(12):30–35Google Scholar
- Galis ZS, Asanuma K, Godin D, Meng X (1998) N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation 97:2382–2383Google Scholar
- Murdock RC, Braydich-Stolle L, Schrand AM, Schlager JJ, Hussain SM (2008) Characterization of nanomaterial dispersions in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol Sci; Epub ahead of printGoogle Scholar
- Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W, Lai D et al (2005b) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8. doi: 10.1186/1743-8977-2-8 PubMedCrossRefGoogle Scholar
- Oberdörster G (2005c) Inhaled Nano-sized particles: potential effects and mechanisms. Compute-renu du first international symposium on occupational health implications of nanomaterials, 12–14 October 2004, Buxton, Great Britain, pp 65–71. Edited by the Health and Safety Executive, Great-Britain and the National Institute for Occupational Safety and Health, USA, July 2005Google Scholar
- Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB, Colvin VL (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92(1):174–185. doi: 10.1093/toxsci/kfj197 PubMedCrossRefGoogle Scholar