Erythrocyte Membrane-Cloaked and Alendronate-Loaded Hollow Prussian Blue Nanoparticles for Synergistic Osteoporosis Therapy via Antioxidant and Targeted Delivery Mechanisms.

Osteoporosis (OP), characterized by reduced bone mass and microstructural deterioration, poses a significant global health burden. Current therapies, such as bisphosphonates (e.g., alendronate, Aln), face challenges, including low bioavailability, systemic toxicity, and lack of targeting. Herein, we developed an erythrocyte membrane (EM)-cloaked Prussian blue (PB) nanoparticle system (EAP) coloaded with Aln to address these therapeutic bottlenecks. The hollow PB core functions as a peroxidase-mimetic catalyst, efficiently scavenging reactive oxygen species (ROS) through Fe3+/Fe2+ redox cycling. Meanwhile, the EM cloaking endows the system with prolonged blood circulation and active bone targeting via integrin receptor-mediated recognition. The EAP exhibits pH-responsive drug release profiles and significant ROS elimination capacity (H2O2: 82.9%; ·OH: 80.2%; O2·-: 85.1%). The EAP can regulate in vitro osteoclast-osteoblast balance by suppressing osteoclastogenesis and promoting osteoblast mineralization. In an ovariectomized aged mouse model, EAP treatment restored bone density and trabecular microarchitecture comparable to sham controls, with histological analysis demonstrating no observable systemic toxicity. Transcription and protein expression analysis revealed downregulated NF-κB/MAPK signaling and osteoclast-specific markers after EAP treatment. This biomimetic nanodelivery system integrates ROS scavenging and targeted drug delivery, providing a potential strategy for OP therapy and other inflammatory bone disorders.