Sonoactivated Cascade Fenton Reaction Enhanced by Synergistic Modulation of Electron–Hole Separation for Improved Tumor Therapy

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.