Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy.

Abstract

Sonodynamic therapy (SDT) has attracted widespread interest in biomedicine, owing to its novel and noninvasive therapeutic method triggered by ultrasound (US). Herein, the Ti₃C₂ MXene nanosheets (Ti₃C₂ NSs) are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment. With the high-temperature treatment, the oxygen defect of Ti₃C₂ MXene nanosheets (H-Ti₃C₂ NSs) is greatly increased. Therefore, the electron (e^-) and hole (h⁺) generated by US can be separated faster due to the improved degree of oxidation, and then the recombination of e^--h⁺ can be prevented with the abundant oxygen defect under US irradiation, which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti₃C₂ NSs without high-temperature treatment. After PEGylation, the H-Ti₃C₂-PEG NSs show good stability and biocompatibility. <i>In vitro</i> studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti₃C₂-PEG NSs, which can improve the SDT efficacy. <i>In vivo</i> studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment, showing photothermal therapy (PTT) enhanced SDT. Most importantly, the H-Ti₃C₂-PEG NSs can be biodegraded and excreted out of the body, showing no significant long-term toxicity. Our work develops the defective H-Ti₃C₂ NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer, extending the biomedical application of MXene-based nanoplatforms.