Objective The toxic effects of indium tin oxide nanoparticles (ITO NPs) on RAW264.7 macrophages, including cell viability, oxidative stress, and inflammatory cytokine release, were studied in order to elucidate the underlying mechanisms of ITO NPs-induced cytotoxicity.

Methods RAW264.7 cells were treated with ITO NPs at 0, 50, 100, and 200 μg/mL to assess RAW264.7 cellular activity, oxidative stress, and the release of inflammatory factors. The changes in cellular substructures were observed by transmission electron microscopy, and the modulatory role of oxidative stress in the cytotoxicity of ITO NPs on RAW264.7 cells was explored by pretreatment with N-acetylcysteine (NAC).

Results At 100 μg/mL, ITO NPs showed significant toxicity to RAW264.7 cells. Phagocytosis of ITO NPs by RAW264.7 cells led to mitochondrial damage and the formation of secondary lysosomes, enhanced oxidative stress response, and promoted the release of pro - inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). NAC pretreatment attenuated the oxidative stress and pro-inflammatory cytokine production levels induced by ITO NPs in RAW264.7 cells.

Conclusions The phagocytosis of ITO NPs by RAW264.7 cells resulted in direct toxicity, and the significant oxidative stress and pro-inflammatory cytokine production might be key mechanisms underlying the toxic effects of ITO NPs.