Inflammation and gene expression in the rat lung after instillation of silica nanoparticles: Effect of size, dispersion medium and particle surface charge

• Silica particles (50 nm) caused significantly more inflammation than 200 nm in the lung.
• Phagocytosis of some types of particles was reduced using BSA as a dispersant.
• Particle size was important in determining Nrf2 expression.
• Inflammatory effects of silica can be modulated by the dispersion medium.

We investigated the effects of silica particles and nanoparticles (NPs) (50 nm and 200 nm) with a neutral and positively charged surface when dispersed in saline, bovine serum albumin (BSA) or lung lining fluid (LLF) 24 h post instillation into the lungs of rats. There was a significant increase in the recruitment of neutrophils in animals instilled with 50 nm plain and aminated NPs compared with 200 nm particles when dispersed in saline or BSA, but not when dispersed in LLF. There was no evidence of toxicity or an increase in the albumin content of the bronchoalveolar lavage fluid. Immunostaining for the transcription factor Nrf2 in BAL cells indicated that there was a significant increase in nuclear colocalisation in animals treated with plain and aminated 50 nm NPs compared with plain and aminated 200 nm particles when dispersed in saline, but no difference was observed between 50 nm and 200 nm aminated particles when dispersed in BSA. There was no difference in nuclear colocalisation with any of the particle types dispersed in LLF. This study suggests that low dose intratracheal exposure to silica nanoparticles can produce an acute inflammatory response and that the dispersion medium may influence the magnitude of this response.