Bone-targeted calcification-photothermal nanoplatform for synergistic tumor ablation and bone regeneration in breast cancer bone metastasis

Breast cancer bone metastasis is a common and devastating complication among patients with advanced breast cancer, marked by aggressive tumor growth and extensive osteolytic destruction. Effective treatment requires simultaneous elimination of tumor cells and restoration of bone tissue. To address this challenge, we developed a bone-targeting nanomaterial, CPPA NPs, composed of a polydopamine-coated calcium peroxide core embedded with palladium nanoparticles, and functionalized with phytic acid for bone affinity. This design integrates calcification and photothermal activity to achieve synergistic tumor inhibition and bone repair. Within the acidic tumor microenvironment, CPPA NPs release Ca²⁺ and H₂O₂, triggering mitochondrial calcium overload and oxidative stress in cancer cells. In the presence of exogenous phosphate, this process drives extensive tumor cell calcification, substantially reducing cell viability. Under 808 nm laser irradiation, the photothermal effect accelerates Ca²⁺ and H₂O₂ release, further enhancing calcification and inducing widespread tumor cell death. Laser treatment promotes osteoblast differentiation, supporting bone regeneration. In a murine breast cancer bone metastasis model, the combined calcification-photothermal therapy markedly suppressed tumor burden, mitigated osteolytic lesions, and promoted new bone formation. Together, these findings establish CPPA NPs as a promising therapeutic platform capable of integrating potent antitumor efficacy with osteogenic regeneration, offering a dual-functional strategy for the treatment of breast cancer bone metastasis.