Bone-targeting single-atom nanozymes for treating breast cancer bone metastasis via the synergistic effect of mild photothermal and chemodynamic therapy

The clinical management of breast cancer bone metastasis presents a significant therapeutic challenge, primarily due to the inadequate delivery of drugs to the bone microenvironment. To address this issue, this study developed bone-targeting single-atom nanozymes aimed at the targeted treatment of breast cancer bone metastases. These nanozymes were synthesized using a coordination‑carbonation strategy and modified with zoledronic acid (ZOL) to enhance their bone-targeting properties. When administered intravenously in a murine model of breast cancer bone metastasis, they efficiently accumulated in bone tissue. Single-atom iron in the nanozymes efficiently catalyzed the production of hydroxyl radicals (•OH) from hydrogen peroxide (H 2 O 2 ) in the acidic microenvironment created by tumor and osteolysis. Under near-infrared region II (NIR-II) laser irradiation, the nanozymes exhibited mild photothermal properties that enhanced chemodynamic therapy (CDT). This combination resulted in effective tumor cell ablation while simultaneously suppressing osteoclast activity, differentiation, and maturation. The dual synergistic therapy of photothermal and CDT effectively inhibited pathological osteolysis while precisely targeting malignant cells, offering a promising strategy for treating breast cancer bone metastasis.