Crystal Phase-Related Toxicity of One-Dimensional Titanium Dioxide Nanomaterials on Kidney Cells

ACS Appl Bio Mater. 2021 Apr 19;4(4):3499-3506. doi: 10.1021/acsabm.1c00036. Epub 2021 Mar 3.

Abstract

One-dimensional (1D) nanomaterials are widely used in different fields, and the increased application of 1D nanomaterials has drawn concerns about their unknown toxicity. 1D titanium oxide (TiO2) nanomaterials in different crystal phases are commonly applied in environmental remediation and solar energy conversion fields, but these materials pose a threat to human health, especially to the kidneys, an organ with abundant blood flow. To systematically evaluate the cytotoxicity to the kidneys, TiO2 nanofibers with TiO2(B), anatase, and rutile phases, as well as nanorods with anatase and rutile phases were synthesized and added to the culture medium of HK2 cells. Cell counting kit-8 assay, 2',7'-dichlorofluorescin diacetate assay, Hoechst 33342 staining experiments, and quantitative real-time reverse transcription polymerase chain reaction tests were used to explore the renal effects of the as-prepared TiO2 nanomaterials in the short term or long term. In the short-term evaluation, all the added TiO2 nanomaterials were toxic to HK2 cells, and the cytotoxicity was dose-dependent. Rutile TiO2 can widely attach to the cell surface and displays the most serious cell-killing and proapoptotic ability, while anatase induces the most serious oxidative stress. In long-term evaluation, all the as-prepared TiO2 nanomaterials led to epithelial mesenchymal transition (EMT), a mechanism of renal fibrosis. Consistent with the short-term results, rutile induced the most serious EMT. This study indicated that the renal toxicity of 1D TiO2 nanomaterials is crystal phase-dependent and that rutile induced the most significant renal cell injury. Oxidative stress is a crucial but not the only contributor to the renal toxicity of TiO2 nanomaterials in the short term.

Keywords: apoptosis; crystal phase; epithelial mesenchymal transition; kidney toxicity; one-dimensional titanium dioxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Humans
  • Materials Testing
  • Nanostructures / chemistry*
  • Particle Size
  • Reactive Oxygen Species / analysis
  • Reactive Oxygen Species / metabolism
  • Titanium / chemistry
  • Titanium / pharmacology*

Substances

  • Biocompatible Materials
  • Reactive Oxygen Species
  • titanium dioxide
  • Titanium