Piezoelectric-driven immunosuppressive remodeling: Ferroptosis/macrophage reprogramming for tumor therapy

Ferroptosis has emerged as a promising strategy for enhancing tumor immunogenicity. However, a major obstacle to the efficacy of ferroptosis-based immunotherapy is the immunosuppressive tumor microenvironment, particularly the dominance of tumor-associated macrophages (TAMs) exhibiting the M2 phenotype. These M2 macrophages secrete immunosuppressive factors, limiting the therapeutic potential of ferroptosis. To overcome these challenges, hollow Te/PtTe 2 inducers were designed to enhance immunotherapy induced by ferroptosis. The unique hollow structure of Te/PtTe 2 inducers effectively captures mechanical energy, promotes efficient electron-hole separation, and triggers reactive oxygen species (ROS) storms within tumor cells. Simultaneously, Te/PtTe 2 inducers synergistically deplete intracellular GSH in combination with ROS storm effects, triggering ferroptosis and releasing damage-associated molecular patterns, enhancing tumor immunogenicity. Additionally, Te/PtTe 2 inducers reshape the immunosuppressive microenvironment under US irradiation by increasing mature dendritic cells, promoting CD8 + T cell infiltration, and reducing immunosuppressive M2 macrophages. Collectively, this work provides a piezoelectric enhancement strategy to overcome immunosuppressive barriers and improve the clinical effectiveness of ferroptosis in cancer treatment.