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.