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

Abstract

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.

Tumor Microenvironment‐Related Sonodynamic Therapy Mediates Tumor Therapy

“…On the one hand, ST can reduce the internal glucose of tumors and reduce the energy source of tumor cells. CAT and CAT-like activity Au-rGO-ZnO@PVP, PMR, PEBVO@PEGNRS, Bac@ARS, SPNC, PB+Ce6@Hy, Ce6-MnO 2 -PVs, YHM, Cu 2 O-CNX@CeO 2 , CAT@HA-HMME NPs [51,53,54,156,157,158,159,160,161,162] Consumption of GSH AIMP [163] Catalytic CDT Mn 3 O 4 /OCN-PPIX@BSA, G-IrTe 2 [164,165] Suppress GSH generation BMP-BSO [166] Consumption of GSH, catalytic CDT UPFB, mZMD NCs, MO@FHO, AIPH@Cu-MOF [52,55,84,85] Consumption of GSH, catalytic ST CPCs@PEG [167] Reverse immunosuppression HABT-C@HA, MFC [168,169] Catalytic ST PPGE NCs [50] Consumption of GSH, catalytic CDT, catalytic ST MPG [170] pH-response DOX@PCN-224/Pt NPs [171] Carry oxygen Reverse immunosuppression TL@HPN(PAI/USI), DMXAAS [172,173] ICG-DOX NPs/PFH@SP94-Lip, SAFE [174,175] Autogeneration of oxygen Chl (MChl) [176] Reduce HIF-1𝛼 M@C [73] Reduce HIF-1𝛼 Relieve hypoxia P-BTO [71] IR780@INPS-CTX, IRP-NPs [177,178] Hypoxia-response ZTC, MCA, C-TiO 2 /TPZ@CM [77,179,180] Catalytic CDT Cu-MOF NPs [75] CAT activity hMVS [78] On the other hand, the produced H 2 O 2 can be used as the substrate of CDT and catalase to catalyze the formation of ROS and oxygen. [56]…”

Rodlike nanomaterials from organic diradicaloid with high photothermal conversion capability for tumor treatment

“…[6][7][8][9][10] To boost the therapeutic effect of PTT, researchers are working on the development of various PTAs, including inorganic and organic ones. [11][12][13][14][15][16] Compared with inorganic ones, organic PTAs are featured with the merits of good biocompatibility and flexibility for structure design and modulating light absorption, thus becoming ideal alternatives for PTT. [17][18][19] To increase the penetration depth of laser and improve the PTT effect of PTAs, intense absorption in the near-infrared (NIR) region and high photothermal conversion efficiency (PCE) are desirable.…”

“…[ 6–10 ] To boost the therapeutic effect of PTT, researchers are working on the development of various PTAs, including inorganic and organic ones. [ 11–16 ] Compared with inorganic ones, organic PTAs are featured with the merits of good biocompatibility and flexibility for structure design and modulating light absorption, thus becoming ideal alternatives for PTT. [ 17–19 ]…”

Near-Infrared-II-Activatable Self-Assembled Manganese Porphyrin-Gold Heterostructures for Photoacoustic Imaging-Guided Sonodynamic-Augmented Photothermal/Photodynamic Therapy

“…Therefore, in addition to early diagnosis, efficient and accurate treatment still remains an important problem to be solved. , With the rapid development of nanoscience, many noninvasive therapeutic methods based on nanomedicine have been developed . Among these, cytotoxic reactive oxygen species (ROS)-mediated nanodynamic therapy can induce irreversible cellular oxidative damage and apoptosis and has drawn much attention as an advanced therapeutic modality. − For instance, photodynamic therapy (PDT) is a noninvasive and spatiotemporally controllable therapy that produces ROS upon irradiation of photosensitizers with near-infrared (NIR) light in the presence of oxygen. , However, the poor penetration depth significantly limits the application of PDT, especially for deep-seated tumors . Recently developed sonodynamic therapy (SDT) is another noninvasive treatment modality that uses ultrasound (US) to activate sonosensitizers to interact with the surrounding oxygen and produce highly cytotoxic ROS to induce apoptosis .…”