Unlocking flexoelectricity in two-dimensional CuAl-LDH nanosheets for ultrasound-driven flexocatalytic tumor therapy

2D centrosymmetric CuAl-LDH as flexocatalysts for sono-flexocatalytic tumor therapy. • Non-uniform lattice distortion induces a strain gradient and flexoelectricity. • Ultrasound-driven generation of superoxide anions, singlet oxygen, and H 2 O 2 . • POD-like activity and GSH depletion synergistically amplify tumor oxidative stress. Sonocatalytic therapy has emerged as a promising antitumor modality owing to its deep tissue penetration and high spatiotemporal accuracy. However, the rapid electron–hole recombination in sonocatalysts severely restricts the reactive oxygen species (ROS) production and therapeutic efficacy. Although piezoelectric materials enable efficient charge separation, their prerequisite of a non-centrosymmetric crystal structure severely constrains the availability of suitable candidates. Herein, we demonstrate that two-dimensional (2D) CuAl-LDH nanosheets, synthesized via a facile coprecipitation route, serve as flexoelectric nanoagents for ultrasound-driven tumor treatment. Under ultrasound stimulation, the nanosheets efficiently generate superoxide anions (·O 2 − ) and singlet oxygen ( 1 O 2 ) through the flexocatalytic effect, alongside simultaneous in situ H 2 O 2 production. Density functional theory calculations reveal that compressive stress creates non-uniform strain gradients that break local inversion symmetry in 2D CuAl-LDH, inducing an in-plane flexoelectric polarization and built-in electric field that synergistically promote charge separation and directional carrier migration. Moreover, the CuAl-LDH nanosheets exhibit intrinsic peroxidase-like activity and glutathione-depleting ability; the ultrasound-generated H 2 O 2 is continuously catalyzed to produce hydroxyl radicals, thereby establishing a cascade ROS-amplification loop that synergistically amplifies intracellular oxidative stress. Furthermore, the nanosheets exhibit favorable biodegradability and biosafety. This work uncovers the intrinsic flexoelectric effect in CuAl-LDH nanosheets and provides insights for the design of 2D LDH-based flexocatalytic nanoplatforms for tumor therapy. 2D centrosymmetric CuAl-LDH nanosheets are developed as flexocatalysts for sono-flexocatalytic tumor therapy. Under ultrasound stimulation, non-uniform lattice distortion induces a strain gradient, leading to flexoelectric polarization that drives the generation of superoxide anions, singlet oxygen, and H 2 O 2 . Additionally, the nanosheets exhibit POD-like activity and deplete GSH, synergistically amplifying intratumoral oxidative stress to enhance antitumor efficacy. Download: Download high-res image (290KB) Download: Download full-size image