Boosting the Sonodynamic Cancer Therapy Performance of 2D Layered Double Hydroxide Nanosheet-Based Sonosensitizers Via Crystalline-to-Amorphous Phase Transformation

Sonodynamic therapy (SDT) has been a promising therapeutic modality for cancer because of its superior advantages compared with other therapeutic strategies. However, the current sonosensitizers used for SDT normally exhibit low activity for ultrasound (US)-induced reactive oxygen species (ROS) generation. Herein, the crystalline-to-amorphous phase transformation is reported as a simple but powerful strategy to engineer ultrathin 2D CoW-LDH and NiW-LDH nanosheets as highly efficient sonosensitizers for SDT. The phase transformation of CoW-LDH and NiW-LDH nanosheets from polycrystalline to amorphous ones is achieved through a simple acid etching treatment. Importantly, compared with the polycrystalline one, the amorphous CoW-LDH (a-CoW-LDH) nanosheets possess higher ROS generation activity under US irradiation, which is ≈17 times of the commercial TiO₂ sonosensitizer. The results suggest that the enhanced performance of ultrathin a-CoW-LDH nanosheets for US-induced ROS generation may be attributed to the phase transformation-induced defect generation and electronic structure changes. After polyethylene glycol modification, the a-CoW-LDH nanosheets can serve as a high-efficiency sonosensitizer for SDT to achieve cell death in vitro and tumor eradication in vivo under US irradiation.