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

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.