Non-central symmetric 2D bismuth-based perovskites for piezoelectric-enhanced sonodynamic immunotherapy

Sonodynamic therapy (SDT), an emerging treatment modality, exhibits great potential in cancer therapy owing to its excellent tissue penetration, immune activation ability, and relatively low side effects. The lattice distortion of inorganic perovskite is challenging to control, which leads to an unsatisfactory SDT effect. This study presents a two-dimensional bismuth-based halide perovskite material, MA₃Bi₂Cl₉-PEG (MBCP), with favorable piezoelectric properties, being first applied to tumor sonodynamic immunotherapy. By introducing methylamine cations, the central symmetry of MBC is effectively disrupted, resulting in a non-centrosymmetric crystal structure. This structural modification remarkably enhances the piezoelectric performance, enabling more robust charge separation effects under ultrasound excitation and thus facilitating the efficient generation of reactive oxygen species (ROS). Moreover, the generated ROS triggers immunogenic cell death in tumor cells, through the depletion of excessive glutathione and the inhibition of glutathione peroxidase 4, induces ferroptosis. The combined therapeutic strategy substantially enhances the anti-tumor efficacy and effectively suppresses lung metastasis. This research offers a promising example of the application of perovskite piezoelectric materials in sonodynamic immunotherapy.