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

Abstract 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 TiO 2 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.