Crystal structure mediates mode of cell death in TiO2 nanotoxicity

Laura K. Braydich-Stolle, Nicole M. Schaeublin, Richard C. Murdock, Jingkun Jiang, Pratim Biswas, John J. Schlager, Saber M. Hussain

Research output: Contribution to journalArticlepeer-review

189 Scopus citations


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).

Original languageEnglish (US)
Pages (from-to)1361-1374
Number of pages14
JournalJournal of Nanoparticle Research
Issue number6
StatePublished - Aug 2009
Externally publishedYes


  • Crystallinity
  • EHS
  • Health effects
  • Keratinocytes
  • Nano-size
  • Nanotechnology
  • Nanotoxicity

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Chemistry(all)
  • Modeling and Simulation
  • Materials Science(all)
  • Condensed Matter Physics


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