Hollow cerium oxide nanoparticles promote M2 polarization and modulate the SLC7A11/GSH/GPX4 axis to attenuate macrophage ferroptosis for inflammatory wound repair

• Dual-functional hollow cerium oxide nanoparticles promote M2 macrophage polarization and concurrently inhibit ferroptosis. • Hollow cerium oxide nanoparticles upregulate the SLC7A11/GSH/GPX4 pathway to suppress ferroptosis. • In vivo , Hollow cerium oxide nanoparticles accelerate inflammatory wound healing. The healing of inflammatory wounds is closely linked to immune regulation. Polarizing macrophages toward the anti-inflammatory M2 phenotype represents a promising strategy for repairing inflammatory wounds. However, macrophages in inflammatory environments exhibit high ferroptosis susceptibility, leading to reduced cellular activity and consequent dysregulation of immune function, which impedes wound repair. Therefore, developing an approach that simultaneously promotes M2 polarization and inhibits macrophage ferroptosis is critical for effective inflammatory wound healing. In this study, multifunctional hollow cerium oxide nanoparticles ( h CeO 2 NPs) were synthesized. h CeO 2 NPs effectively cleared reactive oxygen species (ROS) via enzyme-mimetic activity, thereby promoting M2 macrophage polarization. More important, they upregulated the SLC7A11/GSH/GPX4 pathway by enhancing intracellular glutathione (GSH) and GPX4 expression, thus suppressing macrophage ferroptosis. In vivo results further confirmed that h CeO 2 NPs accelerated inflammatory wound closure by simultaneously promoting M2 polarization and inhibiting ferroptosis. These findings demonstrate that h CeO 2 NPs provide an effective nanotherapeutic strategy for inflammatory wound repair through synergistic modulation of macrophage polarization and ferroptosis susceptibility.