Synergistic Electron Modulation and Cavitation Enhancement of Piezoelectric Sonodynamic for Anti-Tumor Therapy

Piezoelectric sonodynamic therapy (SDT) is a novel non-invasive and highly penetrating cancer treatment method, which can be triggered by ultrasound (US) to induce energy band tilting of piezoelectric sonosensitizers to promote the generation of reactive oxygen species (ROS). However, it remains a challenge to modulate the energy band structure of piezoelectric sonosensitizers to overcome the energy barriers for efficient ROS production at limited US power. Here, Na_0.5Bi_0.5TiO₃ clad with platinum (NBT@Pt) is designed through interface engineering to enhance its piezoelectric properties by leveraging the built-in electric field created between the noble metal Pt and the centrosymmetric semiconductor NBT, thereby breaking the inversion symmetry of the material. Meanwhile, O₂ can be generated from the decomposition of H₂O₂, catalyzed by Pt NPs in the tumor microenvironment, which increases the cavitation strength by 143.5%, resulting in higher piezoelectric potential and piezoelectric catalytic performance of NBT@Pt. Cellular and animal experiments show that NBT@Pt has good biocompatibility and high antitumor efficiency, which show the high tumor inhibition rate as 92.8%. In this study, a novel modulation strategy of piezoelectric sonosensitizers is developed, which provides a typical example for the development of piezoelectric sonosensitizers in the field of anti-tumor therapy.