A single instillation of amorphous silica nanoparticles induced inflammatory responses and tissue damage until day 28 after exposure

Synthetic amorphous silica nanoparticles (SiNPs) are seeing increased and widespread application in diagnosis, imaging, and drug delivery. In the present study, the inflammatory responses and histopathological changes caused by inflowing of SiNPs into the lung were studied in mice after a single intratracheal instillation. Changes in gene expression were also investigated in lung tissue using microarray analysis. As results, weight gain was significantly decreased in SiNP-treated mice on day 1 and 7 after instillation. The secretion of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α] and transforming growth factor (TGF)-β were also increased, and the distribution of cytotoxic T cells, natural killer (NK) cells, and natural killer T (NKT) cells with G1 arrest were increased. Microgranulomatous changes were observed on day 7 and 14. Furthermore, the gene expression was significantly affected on day 7. A total of 331 genes were up-regulated more than 2 fold, and 128 genes were down-regulated more than 2 fold. The secretion of inflammatory related cytokines, histopathological abnormalities, and the severity of gene expression changes decreased in a time-dependent manner. Based on these results, we suggest that SiNPs induce subchronic inflammatory responses and tissue damage in mice after a single intratracheal instillation.