Membrane-coated Prussian blue nanocomplex with enhanced enzyme-mimic activity alleviates senile osteoporosis by reducing osteoprogenitor cell senescence and macrophage inflammation

Senile osteoporosis (SOP) is a chronic age-related skeletal disorder characterized by progressive bone loss and high fracture risk, with pathogenesis linked to excessive reactive oxygen species (ROS), osteoprogenitor cell senescence, and macrophage inflammation. Prussian Blue (PB) nanozymes show antioxidative potential for SOP but are limited by poor targeting, short circulation time, and unclear mechanisms, restricting clinical translation. Herein, we fabricated macrophage membrane-camouflaged citrate-modified PB (M@CPB) nanozymes for targeted SOP therapy and elucidated the underlying mechanism. Macrophage membrane coating prolonged the blood half-life of M@CPB by 1.47-fold and enhanced its bone tissue accumulation by 3.09-fold relative to CPB. In vitro, M@CPB inhibited O₂⁻ by 42.17% and scavenged H 2 O 2 by 22.38%, reduced osteoprogenitor cell senescence, promoted M1-to-M2 macrophage polarization, and decreased the secretion of receptor activator of nuclear factor-κB ligand (RANKL) and tumor necrosis factor-α (TNF-α) to 47.41% and 53.10% of the model group, respectively. In vivo, M@CPB increased bone volume/tissue volume ratio by 3.83-fold relative to SOP mice, effectively ameliorating bone loss, motor dysfunction, and depressive-like behaviors. Collectively, M@CPB mitigated SOP by intervening in the ROS-senescence-inflammation axis and balancing bone remodeling, providing an innovative therapeutic strategy for SOP and potentially other age-related disorders.