Synergistic photothermal-immuno-osteogenic therapy of breast cancer bone metastasis using an icariin-bioactive glass hydrogel

Breast cancer bone metastasis remains a formidable clinical challenge because its pathology involves not just tumor growth, but also osteolytic bone destruction and local immunosuppression—yet current therapies target only one or two of these components. We engineered an injectable hydrogel (ICA@BG-pTA/CMCS/O-HA) that integrates icariin (ICA), bioactive glass (BG), and photothermal tannic acid‑iron nanoparticles in a carboxymethyl chitosan/oxidized hyaluronic acid matrix. Near-infrared irradiation generates localized hyperthermia to ablate tumor cells directly. Concurrently, sustained ICA release promotes osteoblast differentiation, suppresses osteoclast activity, and shifts macrophages from M2 to M1 phenotype, increasing CD8 + T cell infiltration. BG-released Ca 2+ /Si 4+ ions further enhance osteogenesis. In a murine tibial metastasis model, the hydrogel plus NIR irradiation significantly inhibited tumor growth, reversed the immunosuppressive microenvironment, and attenuated osteolytic bone destruction while promoting early bone repair. This platform demonstrates the potential of an integrated photothermal–immuno–osteogenic strategy for breast cancer bone metastasis.