Defect‐Rich 2D Layered Double Hydroxides Enhance Sonodynamic Antibacterial Therapy

Sonodynamic Therapy (SDT) is a non-invasive therapeutic strategy for combating antibiotic-resistant infections. However, current sonosensitizers typically show limited reactive oxygen species (ROS) output under ultrasound (US) irradiation. While layered double hydroxides (LDHs) feature tunable architectures and favorable biocompatibility for biomedical applications, their potential in SDT-driven antibacterial systems remains underexplored. Here, we introduce a defect engineering paradigm based on a facile acid-etching method to construct defect-rich 2D DR-ZnCuW-LDH nanosheets. This ambient-condition approach enables flexible defect-phase engineering without energy-intensive processing. Through this straightforward treatment, the nanosheets undergo a crystalline-to-polycrystalline phase transition, form abundant defects with oxygen vacancies (OVs), and narrow the bandgap (Eg) from 3.29 to 1.80 eV, thereby markedly improving electron-hole separation. Remarkably, DR-ZnCuW-LDH nanosheets exhibit a fourfold increase in ROS generation under US irradiation compared to pristine ZnCuW-LDH, significantly enhancing its performance as an inorganic sonosensitizer for antibacterial applications. This substantial improvement stems from strategically introduced defects and the phase transformation-induced electronic structure modification. Both in vitro and in vivo evaluations validate the exceptional antibacterial efficacy of DR-ZnCuW-LDH nanosheets under US, establishing a versatile platform for sonodynamic antibacterial applications.