Sonoactivated Cascade Fenton Reaction Enhanced by Synergistic Modulation of Electron-Hole Separation for Improved...

Chemodynamic therapy (CDT) is an emerging targeted treatment technique for tumors via the generation of highly cytotoxic hydroxyl radical (·OH) governed by tumor microenvironment-assisted Fenton reaction. Despite high effectiveness, it faces limitations like low reaction efficiency and limited endogenous H₂ O₂ , compromising its therapeutic efficacy. This study reports a novel platform with enhanced CDT performance by in situ sono-activated cascade Fenton reaction. A piezoelectric g-C₃ N₄ (Au-Fe-g-C₃ N₄ ) nanosheet is developed via sono-activated synergistic effect/H₂ O₂ self-supply mediated cascade Fenton reaction, realizing in situ ultrasound activated cascade Fenton reaction kinetics by synergistic modulation of electron-hole separation. The nanosheets consist of piezoelectric g-C₃ N₄ nanosheet oxidizing H₂ O to highly reactive H₂ O₂ from the valence band, Fe³⁺ /Fe²⁺ cycling activated by conduction band to generate ·OH, and Au nanoparticles that lower the bandgap and further adopt electrons to generate more ¹ O₂ , resulting in improved CDT and sonodynamic therapy (SDT). Moreover, the Au-Fe-g-C₃ N₄ nanosheet is further modified by the targeted peptide to obtain P-Au-Fe-g-C₃ N₄ , which inhibits tumor growth in vivo effectively by generating reactive oxygen species (ROS). These results demonstrated that the sono-activated modulation translates into a high-efficiency CDT with a synergistic effect using SDT for improved anti-tumor therapy.