Dual-Gating Strategy: Ultrasound Activation of TRPV2 Channels and Borate-Glass-Induced Calcium Overload for Tumor Suppression.

Effective and precise treatment of breast cancer, particularly with bone metastasis, remains a significant challenge. Here, a dual-gating strategy combining locally delivered borate glass (BG) and ultrasound (US) is developed for the precise and effective inhibition of breast cancer by targeting transient receptor potential vanilloid 2 (TRPV2). The results demonstrate that after local delivery of BG to the solid tumor, US effectively triggers calcium overload by activating the overexpressed TRPV2 channels, leading to mitochondrial autophagy and apoptosis in breast cancer cells, thereby inhibiting tumor growth with high precision. These effects are validated in subcutaneous, orthotopic, and TRPV2-overexpressing breast cancer mouse models. In the bone metastasis model, BG combined with US treatment simultaneously suppresses tumor growth and promotes bone regeneration. Overall, this dual-gating strategy offers a safe and efficient approach for the precise treatment of cancers with high TRPV2 expression and provides new insights into the design and clinical translation of calcium-overload-based cancer therapies.