The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure

Background: Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized. Methods: A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 mu g/ml) of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope. Results: TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (gamma(ads)) increased in a dose-dependent manner from 28.2 +/- 2.3 mN/m to 33.2 +/- 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (gamma(min)) slightly increased from 4.8 +/- 0.5 mN/m up to 8.4 +/- 1.3 mN/m (p < 0.01) at high TiO2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both gamma(ads) (63.6 +/- 0.4 mN/m) and gamma(min) (21.1 +/- 0.4 mN/m). Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae. Conclusion: TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.