Interfacial engineering of Ti₃C₂-TiO₂ MXenes by managing surface oxidation behavior for enhanced sonodynamic therapy

As a kind of reactive oxygen species (ROS) mediated therapy, sonodynamic therapy (SDT) has attracted great interest in cancer therapy. However, highly efficient and biocompatible sonosensitizers are urgently required to improve the therapeutic efficiency of SDT. In this work, Ti₃C₂-TiO₂ MXenes were controllably synthesized as good sonosensitizers through interface engineering by regulating the dissolved oxygen concentration of the aqueous solution. The as-prepared Ar-Ti₃C₂-TiO₂ MXene possessed a narrow band gap of 2.37 eV with promoted charge carrier transformation and efficient electron-hole separation. Compared with pure TiO₂ sonosensitizers, the Ar-Ti₃C₂-TiO₂ MXene displayed higher US-triggered reactive oxygen species (ROS) generation efficiency. In addition, the structurally maintained Ar-Ti₃C₂-TiO₂ possessed good photothermal conversion efficiency and the laser irradiation could greatly improve the electron-hole pair separation efficiency to further increase the ROS generation capability. After modification with arginyl-glycyl-aspartic (RGD) peptide, the Ar-Ti₃C₂-TiO₂-RGD could efficiently accumulate in the tumor sites and achieve effective PTT enhanced SDT to eliminate tumors after intravenous injection without causing appreciable long-term toxicity. Therefore, this work presented a new way to construct safe sonosensitizers for enhanced SDT and the as-prepared Ar-Ti₃C₂-TiO₂-RGD displayed good potential for further clinical translation. STATEMENT OF SIGNIFICANCE: To achieve superior tumor treatment, the nanosized TiO₂/Ti₃C₂ heterostructure was controllably synthesized through interface engineering by regulating the dissolved oxygen concentration of the aqueous solution using inert gas. The oxidation-optimized Ar-Ti₃C₂-TiO₂ MXene possessed good sonodynamic performance with a narrow band gap of 2.37 eV and good photothermal conversion efficiency of 47.3% with structurally maintained Ti₃C₂ MXene. Additionally, the laser irradiation could greatly improve the electron-hole pair separation efficiency to further boost sonodynamic performance of Ar-Ti₃C₂-TiO₂ MXene. Encouragingly, the Ar-Ti₃C₂-TiO₂-RGD could efficiently accumulate in the tumor sites and achieve effective PTT enhanced SDT to eliminate tumors.