Ultrasound‐Driven Piezoelectric Bi‐Ru Heterojunctions for Water‐Splitting Gas Therapy in Tumors

Abstract Cancer treatment faces significant challenges. Piezoelectric therapy has struggled to achieve optimal tumor suppression due to its limitations in piezoelectric material performance. This study therefore designed amphiphilic polyethylene glycol (PEG)‐modified, Bi 2 O 3 /RuO 2 heterojunction composite piezoelectric nanoball flowers (BROP) for tumor gas therapy. Multiple characterization methods demonstrated that BROP efficiently catalyzed water splitting to produce H 2 and O 2 under ultrasound (US) stimulation. Theoretical and experimental studies indicated that construction of the heterostructure increased the material's dipole moment, significantly optimizing charge separation and carrier mobility, enhancing piezoelectric capability, and achieving high catalytic activity. BROP, combined with US, damaged tumor cell mitochondria, induced apoptosis and ferroptosis, and alleviated the hypoxic microenvironment of tumors. Using in vivo tumor models, this therapy achieved a tumor inhibition of 95.2% without damaging major organs. Together, the results of this study facilitated the use of piezoelectric catalytic gas therapy for tumors and provided the basis for the use of inorganic metal piezoelectric sonosensitizers.