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.