Correlating Nanoscale Titania Structure with Toxicity: A Cytotoxicity and Inflammatory Response Study with Human Dermal Fibroblasts and Human Lung Epithelial Cells

TLDR

Nanocrystalline titanium dioxide is widely used and can generate reactive species under UV, enabling applications such as self‑cleaning glass and solar cells. The study aims to characterize the toxicity of nano‑TiO2 under ambient conditions in cell culture. The authors exposed human dermal fibroblasts and lung epithelial cells to nano‑TiO2 at various concentrations and measured cytotoxicity and inflammatory responses. Cytotoxicity and inflammation appeared only at high concentrations (100 µg/ml) with dose‑response and time‑dependent increases; toxicity was independent of surface area but strongly correlated with phase composition, with anatase 100× more toxic than rutile, and the most cytotoxic samples produced the most reactive oxygen species under UV, linking RS production to cellular damage.

Abstract

Nanocrystalline titanium dioxide (nano-TiO2) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 μg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO2, for example, was 100 times more toxic than an equivalent sample of rutile TiO2. The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO2 samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity.