Endogenous/Exogenous Dual‐Responsive Bimetallic Hollow Nanozyme for Photothermal/Nanocatalysis/Immune Synergistic Tumor Therapy

ABSTRACT Nanozymes have attracted considerable attention in cancer therapy due to their adjustable enzyme activity and high catalytic efficiency. However, they still face a major challenge from tumor metastasis. In this work, endogenous/exogenous dual‐responsive bimetallic hollow PdRu (termed HPdRu) nanozymes were prepared. They respond to the tumor microenvironment with weak acidity and overexpressed hydrogen peroxide (H 2 O 2 ), producing large amounts of reactive oxygen species (ROS), including hydroxyl radicals (·OH) and superoxide anions (·O 2 − ). These ROS cause mitochondrial damage and achieve specific nanocatalysis therapy (NCT). Under near‐infrared (NIR) light irradiation, the HPdRu nanozymes exhibit remarkable photothermal conversion ability (48.7%). Heat ablation from NIR light‐mediated photothermal therapy (PTT) and eruptible ROS jointly trigger tumor cell apoptosis. The tumor suppression rate reaches as high as 95%. Moreover, NCT and PTT induce immunogenic cell death through the release of damage‐associated molecular patterns, which stimulate dendritic cell maturation and T lymphocyte activation, thereby inhibiting tumor metastasis. Overall, the bimetallic nanozymes establish an efficient anticancer model through the combined action of NCT, PTT, and immunomodulation, offering new perspectives for malignant tumor treatment.