AIE‐Augmented NIR‐II‐Emissive Supramolecular Metallacycle Nanoplatform for Tumor Microenvironment‐Responsive Chemo‐Photothermal‐Immunotherapy

The integration of multimodal therapies into a single nanoplatform promises significant advances in precision oncology, yet structural instability, premature drug leakage, and insufficient immune activation remain key challenges. Herein, a supramolecular metallacycle‐based nanoplatform ( M2S‐AD NPs) is engineered through coordination‐driven self‐assembly and β ‐cyclodextrin‐mediated host‐guest encapsulation. The metallacycle exhibits aggregation‐induced emission (AIE) characteristics to amplify NIR‐II fluorescence (1084 nm) for real‐time tumor imaging and achieves a record‐high photothermal conversion efficiency (42.7%) under 808 nm irradiation, enabling deep‐tissue photothermal ablation. Leveraging tumor microenvironment (TME)‐responsive disulfide bonds and pH‐labile Pt‐N coordination, M2S‐AD NPs selectively release chemotherapeutic agents in glutathione‐rich tumors while maintaining stability under physiological conditions. Synergistically, localized hyperthermia induces immunogenic cell death, releasing tumor antigens to prime dendritic cells, while co‐delivered anti‐PD‐L1 antibodies reverse immunosuppression, amplifying cytotoxic T lymphocyte infiltration. In 4T1 breast tumor models, this combinatorial strategy eradicates primary tumors and suppresses distant metastases with >80% tumor growth inhibition without inducing systemic toxicity. By unifying AIE‐enhanced imaging, TME‐triggered drug release, and immunomodulation, this work establishes a supramolecular engineering paradigm for next‐generation cancer theranostics, bridging material innovation with immunooncology to combat metastatic malignancies.