Disuse osteoporosis is a significant clinical challenge lacking targeted therapies. This study developed a bone-targeted nanoplatform for osteoblast therapy. A candidate drug was first screened using network pharmacology. Subsequently, siRNA-loaded nanoparticles with a ssPBAE/PLGA/OA (PPO) core were synthesized by ultrasonic emulsification. These were further cloaked with a red blood cell membrane (RBCM) functionalized with a bone-homing (AspSerSer) 6 peptide to create the final targeted (DSS) 6 -RBCM-PPOS nano particle through ultrasonic coating. The nanoparticles were thoroughly characterized and demonstrated high drug loading (95%), efficient cellular uptake, and significant lysosomal escape in MC3T3-E1 osteoblasts. In vitro microgravity cell model, nanoparticles exhibited better ROS clearance and promoting osteogenesis ability. In a disuse osteoporosis mouse model induced by botulinum toxin-induced hindlimb paralysis, treatment with the targeted nanoparticles showed good biocompatibility and significantly improved trabecular bone density and microstructure compared to controls, as confirmed by micro-CT analysis. In conclusion, we successfully developed a multifunctional nanoplatform that exhibits excellent in vitro performance and significant therapeutic efficacy in restoring bone loss, highlighting its great potential for targeted osteoblast therapy in disuse osteoporosis.
Wang et al. (Thu,) studied this question.