Bioinspired Nanoplatform Potentiates Sonodynamic Immunotherapy by Remodeling the Antioxidant Tumor Microenvironment and Activating STING pathway

Background: Sonodynamic therapy (SDT) has emerged as a promising modality for treating deep-seated tumors. It has been demonstrated that SDT effectively induces immunogenic cell death (ICD), thereby initiating a systemic anti-tumor immune response - a process known as sonodynamic immunotherapy. However, its efficacy is severely limited by the hypoxic tumor microenvironment (TME) and elevated glutathione (GSH) levels, which together scavenge reactive oxygen species (ROS) and create a potent antioxidant barrier. Methods: were investigated in a mouse model of colon cancer. Flow cytometry analysis was used to analyze the tumor immune microenvironment. Results: . Notably, it remodeled the tumor immune microenvironment by promoting CD8⁺ T cell infiltration, enhancing the secretion of IFN-γ and TNF-α, and reducing the populations of regulatory T cells and myeloid-derived suppressor cells. Conclusions: /QD@LM confirms the synergistic role of multi-enzyme activities and STING pathway activation in potentiating sonodynamic immunotherapy, and provides an innovative strategy to overcome TME-mediated therapy resistance.