Engineered PB-Mn Nanoplatform Alleviates Bone Loss via Modulating Oxidative Stress and Macrophage Phenotypic Switch

Osteoporosis (OP) regenerative therapy remains challenging due to severe bone microenvironment dysregulation. Prussian blue (PB) is limited to acute diseases for its transient reactive oxygen species (ROS)-clearing effect, while manganese (Mn) exhibits potent antioxidant activity but poor biocompatibility. Herein, we synthesized a novel composite nanoparticle PB-Mn to address these limitations. In vitro experiments showed that PB-Mn efficiently scavenges ROS (H₂O₂, O₂ ^-, •OH) in a dose-dependent manner, enhances antioxidant enzyme (CAT, SOD, POD, GPX) activities, and promotes M1-to-M2 macrophage polarization by reducing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increasing anti-inflammatory factors (IL-4, IL-10). In vivo studies using ovariectomized (OVX) mice confirmed that PB-Mn significantly increases bone mineral density (BMD), improves trabecular structure (trabecular volume fraction, thickness, and surface area), and balances osteoblast-osteoclast activities by alleviating oxidative stress and inflammation. This synergistic nanoplatform (PB for biocompatibility, Mn for enhanced ROS-scavenging) provides a novel strategy for osteoporosis treatment by targeting ROS and immune reprogramming.