Defect-Rich Glassy IrTe2 with Dual Enzyme-Mimic Activities for Sono-Photosynergistic-Enhanced Oncotherapy

The complexity, diversity, and heterogeneity of malignant tumors pose a formidable challenge for antitumor therapy. To achieve the goal of significantly enhancing the antitumor effect, nanomedicine-based synergistic therapy is one of the important strategies. Herein, we innovatively report a defect-rich glassy IrTe₂ (G-IrTe₂) with weak Ir-Te bond strength for synergistic sonodynamic therapy (SDT), chemodynamic therapy (CDT), and mild photothermal therapy (PTT). G-IrTe₂ sonosensitizer under ultrasound (US) stimuli exhibits excellent reactive oxygen species (ROS) production performance. Besides, catalase (CAT)-like activity of G-IrTe₂ can provide abundant oxygen to enhance the SDT effect. Then, the theoretical calculation verifies that US stimuli can easily make the irregular Ir-Te bond to be broken in amorphous IrTe₂ and free electrons will be released to combine with the oxygen and further form singlet oxygen (¹O₂). Meanwhile, G-IrTe₂ with peroxidase (POD)-like activity can also catalyze endogenous H₂O₂ to produce more ROS for chemodynamic therapy (CDT), which is conducive to better tumor ablation. Furthermore, the ROS produced by sono-/chemodynamic processes can cause mitochondrial dysfunction and further give rise to heat shock protein (HSP) downregulated expression, maximizing the efficiency of mild PTT. Therefore, such glassy IrTe₂ with rich defect could be significantly involved in synergistic oncotherapy and then effectively achieve outstanding antitumor efficacy. This study provides a new research idea for expanding the application of inorganic glassy nanomaterials in promoting the therapeutic effect of tumors.