In Situ Synthesis of Ru/TiO_2-x@TiCN Ternary Heterojunctions for Enhanced Sonodynamic and Nanocatalytic Cancer Therapy

Albeit nanozymes-based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)-specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one-step in situ synthesis strategy is reported to construct ternary Ru/TiO2-x@TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2-x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound-activated ROS generation of Ru/TiO2-x@TiCN because of the accelerated electron transfer and inhibits electron-hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2-x@TiCN with triple enzyme-like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2O2 to relieve hypoxia and heterojunction-mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2-x@TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.