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

Abstract Oxygen‐deficient molybdenum oxide (MoO X ) nanomaterials are prepared as novel nanosensitizers and TME‐stimulants for ultrasound (US)‐enhanced cancer metalloimmunotherapy. After PEGylation, MoO X ‐PEG exhibits efficient capability for US‐triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoO X ‐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, MoO X ‐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 MoO X ‐PEG, the combination treatment of MoO X ‐triggered SDT and aCTLA‐4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.