Oxygen‐Deficient Molybdenum Oxide Nanosensitizers for Ultrasound‐Enhanced Cancer Metalloimmunotherapy

• Published in: Angewandte Chemie Vol. 135; no. 9
• Main Authors: Wang, Yuanjie, Gong, Fei, Han, Zhihui, Lei, Huali, Zhou, Yangkai, Cheng, Shuning, Yang, Xiaoyuan, Wang, Tianyi, Wang, Li, Yang, Nailin, Liu, Zhuang, Cheng, Liang
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 20.02.2023
• Subjects: Cancer; Cell death; cGAS-STING Pathway; Chemistry; DC Maturation; Dendritic cells; Depletion; Glutathione; Immunogenicity; Immunology; Irradiation; Maturation; Metalloimmunotherapy; Metastases; Molybdenum; Molybdenum Oxide; Molybdenum oxides; Nanomaterials; Nanotechnology; Oxygen; Radiation; Reactive oxygen species; Robustness; Sonodynamic Therapy; Stimulants; Tumors; Ultrasound
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202215467

Oxygen‐deficient molybdenum oxide (MoOX) nanomaterials are prepared as novel nanosensitizers and TME‐stimulants for ultrasound (US)‐enhanced cancer metalloimmunotherapy. After PEGylation, MoOX‐PEG exhibits efficient capability for US‐triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX‐PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX‐PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS‐STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX‐PEG, the combination treatment of MoOX‐triggered SDT and aCTLA‐4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors. MoOX nanomaterials were prepared as novel sonosensitizers and TME stimulants for ultrasound‐enhanced cancer metalloimmunotherapy. Under US irradiation, they could generate a massive amount of ROS to induce cell damage and strong ICD. MoOX‐PEG itself could also stimulate the maturation of dendritic cells and activate the cGAS‐STING pathway. Thus, MoOX‐triggered SDT combined with aCTLA‐4 could elicit robust immune responses for antitumor therapy.