Selenium nanoparticles efficiently inhibit M1 macrophage polarization by regulating selenoprotein to scavenge ROS in alleviating rheumatoid arthritis.

Excessive reactive oxygen and nitrogen species (RONS) in the rheumatoid arthritis (RA) microenvironment act as key functional signaling molecules that induce M1 polarization of synovial macrophages, leading to an imbalance in the M1/M2 macrophage ratio and accelerating RA progression. Our previous studies found that selenium nanoparticles (Se NPs) effectively alleviate RA symptoms by scavenging intracellular RONS in macrophages. However, the mechanism by which Se NPs regulate macrophage polarization to inhibit RA progression remains unclear. Therefore, we synthesized stable spherical Se NPs. In vivo and in vitro studies found that Se NPs inhibited M1 macrophage polarization and suppressed inflammatory responses by scavenging ROS and suppressing lipid peroxidation to prevent ferroptosis, thereby alleviating RA progression. Further mechanism studies showed that Se NPs directly upregulate the expression of the selenoprotein GPx4 and simultaneously inhibit the expression of surface receptor molecules associated with the NF-κB signaling pathway in M1 macrophages. Thus, Se NPs enhance ROS scavenging efficiency by upregulating selenoprotein expression, which in turn blocks the NF-κB signaling pathway, effectively balancing between M1 and M2 macrophages by inhibiting the polarization of M1 macrophages, resulting in the alleviation of RA progression. This study provides necessary scientific evidence for the bioactivity of Se NPs and offers new strategies for the treatment of RA.