Unleashing the Potential of Metal Ions in cGAS-STING Activation: Advancing Nanomaterial-Based Tumor Immunotherapy

Immunotherapy is a critical modality in cancer treatment with diverse activation pathways. In recent years, the stimulator of interferon genes (STING) signaling pathway has exhibited significant potential in tumor immunotherapy. This pathway exerts notable antitumor effects by activating innate and adaptive immunity and regulating the tumor immune microenvironment. Various metal ions have been identified as effective activators of the STING pathway and, through the design and synthesis of nanodelivery platforms, have been applied in immunotherapy as well as in combination therapies, such as chemotherapy, chemodynamic therapy, photodynamic therapy, and cancer vaccines. Metal nanomaterials showcase unique advantages in immunotherapy; however, there are still aspects that require optimization. This review systematically examines existing metal-based nanomaterials, elaborates on the mechanisms by which different metal ions activate the STING pathway, and discusses their application models in tumor combination therapies. We also provide a comparative analysis of the advantages of metal nanomaterials over other treatment methods. Our exploration highlights the broad application prospects of metal nanomaterials in cancer treatment, offering new insights and directions for the advancement of tumor immunotherapy.