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

Chemodynamic therapy (CDT) is an emerging targetted 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 H O , 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-C N (Au-Fe-g-C N ) nanosheet w as developed via sono-activated synergistic effect/H O self-supply mediated cascade Fenton reaction, realizing in situ ultrasound (US) activated cascade Fenton reaction kinetics by synergistic modulation of electron-hole separation. The nanosheets consisted of piezoelectric g-C N nanosheet oxidizing H O to highly reactive H O from the valence band, Fe /Fe cycling activated by conduction band to generate ·OH, and Au nanoparticles that lowered the band gap and further adopted electrons to generate more O , resulting in improved CDT and sonodynamic therapy (SDT). Moreover, the Au-Fe-g-C N nanosheet w as further modified by the targeted peptide to obtain P-Au-Fe-g-C N , which inhibited 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. This article is protected by copyright. All rights reserved.