A Mixed‑Valence Cu/Mn Bimetallic Coordination Polymer Nano‑Assembly Co‑Loaded With Taurine and Lenvatinib for Synergistic Tumor Chemo‐Metalloimmunotherapy

ABSTRACT Despite considerable progress in cancer immunotherapy, the therapeutic efficacy of current cancer therapy continues to be hampered by the immunosuppressive tumor microenvironment (ITME), which is characterized by acidification, hypoxia, elevated H 2 O 2 levels, and aberrant angiogenesis. While transition metal‐based nanomaterials hold great promise for modulating the ITME, their effectiveness is often constrained by insufficient reactive oxygen species (ROS) generation, low immunogenicity, poor immune cell infiltration, and T‐cell exhaustion. To address these issues, we developed a bimetallic Cu/Mn‐doped nanoplatform, CMPTL, which further integrates acid‐dissociable taurine and the angiogenesis inhibitor lenvatinib for malignant solid tumor therapy. This nanoplatform simultaneously triggers violent ROS and cuproptosis, leading to mitochondrial damage and the release of mitochondrial DNA. The subsequent activation of the cGAS‐STING pathway, synergistically enhanced by Mn 2+ , initiates robust immune responses. Additionally, taurine helps alleviate T‐cell exhaustion, while lenvatinib promotes tumor vessel normalization, leading to comprehensive remodeling of the TIME. Together, these multimodal mechanisms endow CMPTL with potent antitumor activity, positioning it as a promising candidate for cancer therapy.