Selenium-Loaded Calcium Phosphate with Long-Term and Curative Dosage Drug Release for Post-Surgical Osteosarcoma Management and Osteogenesis.

Although neoadjuvant chemotherapy is widely used after osteosarcoma (OS) surgery, suboptimal chemotherapy accelerates OS recurrence, and postoperative bone repair remains challenging. Here, we report a selenium-loaded biomimetic calcium phosphate (Se@BioCaP) to provide a long-term therapeutic-dose release for postoperative OS treatment. Sodium selenite was incorporated into a biomimetic calcium phosphate (BioCaP) via a wet biomimetic mineralization protocol. The release kinetics of Se@BioCaP achieved a transition from non-Fickian transport to Fickian diffusion, delivering sustained cytotoxic concentrations under acidic, tumor-like conditions while maintaining biocompatibility with osteoblasts (OBs) under physiological conditions. The reduction in OS cell viability was associated with the disruption of redox homeostasis, including the downregulation of key antioxidant enzymes (SOD2 and GPx1), increased reactive oxygen species (ROS), and acidic vesicular organelle (AVO) formation. Notably, Se@BioCaP200 extracts maintained in vitro anticancer and pro-osteogenic activity at day 42, while antibacterial activity was maintained through day 42. These findings suggest that Se@BioCaP may be a promising candidate for postoperative OS management.