Centrosymmetry Breaking of Cobalt–Vanadium-Layered Double Hydroxide Nanosheets via Nitrogen Doping for Enhanced Piezocatalytic Tumor Therapy

Abstract Piezocatalysis has emerged as a promising tumor therapeutic strategy because it enables oxygen-independent generation of multiple reactive oxygen species (ROS) with deep tissue penetration. However, the piezocatalytic efficiency of piezoelectric nanomaterials remains constrained by limited lattice distortion, low carrier separation efficiency, and insufficient catalytic active sites. Herein, we report the centrosymmetry breaking of cobalt–vanadium-layered double hydroxide (CoV-LDH) nanosheets via nitrogen doping for efficient ultrasound (US)-mediated piezocatalytic tumor therapy. Owing to the nitrogen doping-induced disruption of the centrosymmetric structure and lattice distortion in CoV-LDH, nitrogen-doped CoV-LDH (N-CoV-LDH) achieves an ultrahigh piezoelectric coefficient of 89.4 pm·V–1, which is superior to that of previously reported piezocatalytic nanomaterials. Moreover, nitrogen doping introduces an unsaturated coordination environment, significantly promoting the adsorption and activation of O2 (Eads = −2.63 eV) and H2O (Eads = −2.37 eV), thereby enhancing piezocatalytic redox reaction kinetics (k > 1.1 × 103 min–1·g–1). Consequently, under low-power US stimulation (0.15 W·cm–2), N-CoV-LDH nanosheets exhibit markedly enhanced ROS generation efficiency, including that of hydroxyl radicals (·OH), superoxide anions (·O2–), and singlet oxygen (1O2). This robust piezocatalytic ROS generation induces tumor cell apoptosis and immunogenic cell death, thereby activating an antitumor immune response characterized by dendritic cell maturation, M1 macrophage polarization, and T cell activation. Ultimately, N-CoV-LDH-mediated piezocatalytic therapy achieves suppression rates of 97.78% for primary tumors and 87.67% for metastatic tumors, establishing an efficient therapeutic paradigm for suppressing tumor metastasis and recurrence.