【Title】Flexoelectricity-boosted core-shell nanoparticles with self-amplified fenton-like activity for tumor piezocatalytic immunotherapy

【Abstract】Piezocatalytic therapy, which utilizes ultrasonic activation of piezoelectric materials to generate reactive oxygen species (ROS), holds significant potential. However, its efficacy is constrained by the limited ROS generation capacity of piezoelectric materials. In this study, a gradient ion replacement strategy was employed to construct Cu_xBa_1-xTiO₃-shell structured BaTiO₃ (Cu-BTO) piezoelectric materials with flexoelectric properties. This process induces the BTO surface to transition from a crystalline state to an amorphous state and subsequently recrystallize. The phase transformation introduces flexoelectric properties in Cu-BTO surface, while the disparity in ionic radii between Cu²⁺ and Ba²⁺ enhances lattice asymmetry. Consequently, Cu-BTO exhibits significantly enhanced piezoelectric and piezocatalytic properties, with the d₃₃ value reaching 129.91 pm/V, representing an increase of 345.93%. Under ultrasonic stimulation, Cu-BTO can not only directly generate ^•OH and H₂O₂ through piezocatalysis, but also achieve self-amplified Fenton-like catalysis and GSH depletion by promoting charge transfer via the built-in electric field. The strong oxidative stress induces severe immunogenic cell death (ICD) of tumor cells, and triggers a series of antitumor immune responses such as dendritic cell (DC) maturation and T cell activation. Ultimately, an 83.7% tumor inhibition rate is achieved, and lung metastasis of the tumor is effectively prevented. This work not only demonstrates a method to describes a method for inducing the flexoelectric effect in piezoelectric nanomaterials but also provides novel insights into the design and optimization of piezoelectric nanomaterials.

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