Size‐dependent superparamagnetic iron oxide nanoparticles dictate interleukin‐1β release from mouse bone marrow‐derived macrophages

: Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated for their biomedical applications in magnetic resonance imaging, targeting therapy, cell labeling, etc. It has been well documented that macrophages produce interleukin (IL)-1β via several signaling pathways, such as inflammasome activation in response to particles including silica, asbestos and urea crystals with lipopolysaccharide priming. However, the size and dose effects of SPIONs on macrophages and the mechanisms remain unclear. In this study, we explored the cytotoxicity and mechanisms of the synthesized SPIONs with different size distributions of 30, 80 and 120 nm, and compared their potential capability in inducing IL-1β release in mouse bone marrow-derived macrophages (BMMs). We found that SPIONs induced IL-1β release in a size- and dose-dependent manner, in which the smallest SPIONs triggered the highest IL-1β in BMMs. When cellular uptake of SPIONs was inhibited by the actin polymerization inhibitor, cytochalasin D, SPION-induced IL-1β release was suppressed in BMMs. Preventing lysosome damage with bafilomycin A1 or CA-074-Me also counteracted SPION-induced IL-1β release. Moreover, SPION-activated IL-1β release was also attenuated by reactive oxygen species scavengers, diphenylene iodonium or N-acetylcysteine. Our results elucidated the effects of size and dose on the cytotoxicity and mechanisms of IL-1β release of SPIONs on macrophages, which facilitate the theoretical and experimental application of SPIONs in biotechnology and biomedicine in the future.