A tumor microenvironment-triggered biomineralized nanoplatform synergizes with lypressin for tumor blockade therapy

• TME-responsive dual therapy: BMNPs/LVP couples tumor-cell biomineralization with LVP-induced vascular infarction to co-block nutrient exchange in osteosarcoma. • Targeted design & trigger: Bisphosphonate-guided accumulation enables acid-triggered membrane insertion, Ca 2+ sequestration, calcified-layer formation, and on-site LVP release. • Superior in vivo efficacy: Versus biomineralization alone, the combo slows tumor growth, curbs metastasis, and prolongs survival in tumor-bearing animals. Clinical outcomes for osteosarcoma remain poor despite surgery and multi-agent chemotherapy. Biomineralization therapy can inhibit tumor growth by nucleating a calcified layer on the cancer cell surface, but its efficacy is limited by residual perfusion and metabolic compensation. Here, we report a tumor-microenvironment (TME)-responsive nanoplatform that integrates biomineralization with vascular infarction. Biomineralization-inducing nanoparticles (BMNPs) are electrostatically complexed with the vascular-blocking agent lysine vasopressin (LVP) to form BMNPs/LVP. In the acidic TME, BMNPs reorganize to chelate Ca 2+ and deposit a pericellular calcified layer while simultaneously releasing LVP. The released LVP induces intratumoral thrombosis and vessel occlusion. This dual blockade synergistically restricts tumor proliferation and metastasis. In osteosarcoma models, BMNPs/LVP outperformed biomineralization monotherapy, yielding slower tumor growth, reduced metastatic burden, and prolonged survival, with favorable biocompatibility. These findings establish a biodegradable, tumor-targeted calcification-inducing nanoplatform combined with vascular infarction as a promising strategy for biomineralization-based cancer therapy