Superparamagnetic iron oxide nanoparticles attenuate lipopolysaccharide-induced inflammatory responses through modulation of toll-like receptor 4 expression

Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively applied in biomedical fields, such as magnetic resonance imaging and as nanocarriers. However, the biosafety of SPIONs is not completely established, especially their effect on the immune system and inflammatory responses. Toll-like receptor (TLR) signaling is essential for many acute and chronic human inflammatory diseases. Regulation of TLR responses with drugs is helpful for these inflammatory conditions. In this study, we investigated the effects of 10 and 30 nm SPIONs on macrophages in the presence or absence of the TLR4 agonist lipopolysaccharide (LPS). We found that SPIONs inhibited the release of inflammatory cytokines induced by LPS both in murine and human macrophages in a concentration-dependent manner. Meanwhile, SPIONs suppressed inducible nitric oxide synthase expression activated by SPIONs in RAW264.7 macrophages. Additionally, TLR4 mRNA transcription and expression were attenuated with SPIONs treatment, which positively correlated with the release of inflammatory cytokines. In summary, our study demonstrates that SPIONs can suppress inflammatory responses, and the underlying mechanism may be regulated by TLR4 expression. Our present work contributes to clarifying the biosafety of SPIONs and provides a potential approach to alleviate human inflammatory diseases.