Hypoxia-amplifying polymer nanoprodrugs for sonodynamic chemotherapy for breast cancer and bone metastasis via in situ thrombogenesis

thrombogenesis in tumor tissues, disrupting vascular functions and oxygen supply to further intensify tumor hypoxia. As a consequence, TPZ prodrugs are activated in aggravated hypoxic regions to enable enhanced chemotherapeutic effects. Remarkably, this therapeutic approach is demonstrated to achieve near-complete eradication of subcutaneous 4T1 breast tumors and substantial inhibition of bone metastasis progression in murine models. Our work presents a novel vascular disruption strategy for hypoxia potentiation, offering a promising therapeutic paradigm for treating hypoxic solid and metastatic tumors.