In-Situ Grown Nanocrystal TiO₂ on 2D Ti₃C₂ Nanosheets with Anti-Tumor Activity from Photo-Sonodynamic Treatment and...

Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti₃C₂ structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti₃C₂ nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H₂O₂ in the tumor microenvironment. This new material can construct Ti₃C₂/TiO₂ heterostructures in vivo.

Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti₃C₂/TiO₂ heterostructure inhibited tumor growth.

Complementarily, our results showed that the Ti₃C₂/TiO₂ heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti₃C₂ nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.

These findings open up new avenues for enhancing 2D Ti₃C₂ nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.