Synergistic Interaction between Metal Single-Atoms and Defective WO_{3- x} Nanosheets for Enhanced Sonodynamic Cancer...

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO_{3- x} nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO₃ and OV-rich WO_{3- x} nanosheets are first prepared by simple calcination of the WO₃·H₂O nanosheets under an air and N₂ atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO_{3- x} nanosheets to obtain metal SA-decorated WO_{3- x} nanocomposites (M-WO_{3- x}). Importantly, the Cu-WO_{3- x} sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO_{3- x} and Cu SA-decorated WO₃, which is also higher than other M-WO_{3- x} nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO_{3- x} nanosheets should be attributed to the synergistic effect between Cu SAs and WO_{3- x} OVs. Therefore, after polyethylene glycol modification, the Cu-WO_{3- x} can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO_{3- x}-mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.