A Potent Nickel‐Based STING Agonist Nanodrug Against Prostate Cancer Bone Metastasis

ABSTRACT Prostate cancer, the most prevalent urogenital malignancy in males, presents clinical challenges due to its bone metastatic propensity and therapeutic resistance. While the cGAS‐STING pathway is an immunotherapeutic target, the physicochemical instability and poor tumor targeting still limit its clinical application. Although transition metal‐based nanodrugs have emerged as potential STING activators, conventional nickel oxide nanoparticles exhibit inadequate immunomodulatory efficacy. To address these limitations, a carbon‐supported nickel oxide nanodrug (C@NiO x ) using atomic layer deposition (ALD) technology was developed in this study. The self‐limiting surface reactions inherent to ALD enable precise dimensional control of nickel‐based nanostructures, while the chemical bonding at the carbon‐metal oxide interface enhances interfacial electron transfer properties, thereby optimizing both catalytic performance and reactive oxygen species (ROS) production efficiency. In vitro and in vivo studies confirm that the C@NiO x nanodrug effectively inhibits primary tumor growth and metastatic dissemination while alleviating cancer‐induced bone pain through a dual mechanism involving ROS‐dependent immunogenic cell death and potent STING pathway activation. This ALD‐based nanotherapeutic strategy establishes a new paradigm for prostate cancer treatment by simultaneously targeting malignant progression and modulating the immunosuppressive bone microenvironment.