Cascade-amplified Oxidative Stress via Bandgap-Tuned KBiO₃ Perovskite for Cancer Therapy

Sonodynamic therapy (SDT) is a promising cancer treatment due to its ability to utilize ultrasound (US) to activate sonosensitizers, generating reactive oxygen species (ROS) for tumor suppression. High-valence bismuth, known for its unique photoacoustic properties and biocompatibility, has shown great potential when combined with SDT. However, conventional sonosensitizers with large bandgaps and electron-hole recombination have limited SDT's effectiveness. Herein, a bismuth-based piezoelectric sonosensitizer is developed, DSPE-PEG 2000-modified KBiO₃ (KBP), which features a reduced bandgap (1.9 eV). This facilitates electron transfer and depletes glutathione in the tumor microenvironment. Under the US, the piezoelectric sonosensitizer KBP generates a significant amount of ROS, leading to cancer cell pyroptosis via the ROS-NLRP3-Caspase-1-GSDMD pathway. Both in vitro and in vivo experiments demonstrated that the piezoelectric SDT treatment can effectively inhibit tumor growth. This research offers a novel approach to cancer treatment by leveraging the advantages of piezoelectric SDT, demonstrating promising clinical potential for tumor inhibition.