A targeted and core-shell structured gambogic acid nanomedicine for ameliorating breast cancer-associated osteolysis

The treatment of breast cancer-associated bone tumors is of critical importance and highly challenging, primarily owing to the malignant interplay between tumor proliferation and osteolysis within the bone tumor microenvironment. Although many efforts have been devoted, it is still urgent and desirable to find a robust therapeutic agent that can simultaneously and efficiently inhibit the proliferation of bone tumor and osteoclast differentiation. In this work, we have fabricated a bone-targeting nanoplatform based on bioinspired polydopamine-coated gambogic acid nanoparticles (GA@PDA NPs) integrated with mild temperature photothermal therapy (PTT) and chemotherapy towards the treatment of bone tumors. In particular, GA not only inhibits osteoclast differentiation and proliferation of bone tumor cells, but also downregulates heat shock protein 90 (Hsp90) in the treated tumor cells to sensitize the PTT effect, and the resulting core-shell structured nanomedicine could allow the spatiotemporal control of chemotherapy and mild temperature PTT. Those bioinspired nanomedicine could exhibit excellent tumor suppression and osteolysis inhibition against a xenograft tumor bone metastasis model, and this novel nanoformulation provides a creative paradigm for the treatment of breast cancer-associated osteolysis.