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Mn<jats:sup>2+<\/jats:sup>\u2010mediated activation of interferon gene stimulator (STING) pathway provides an alternative for combination radioimmunotherapy of tumor. However, it is still a challenge for specific delivery of Mn<jats:sup>2+<\/jats:sup> to innate immune cells and targeting activation of STING pathway. Herein, a novel antigen\u2010inspired MnO<jats:sub>2<\/jats:sub> nanovaccine is fabricated as Mn<jats:sup>2+<\/jats:sup> source and functionalized with mannose, enabling it to target innate immune cells to activate the STING pathway. Meanwhile, the release of Mn<jats:sup>2+<\/jats:sup> in the intracellular lysosomes can also be for magnetic resonance imaging to monitor the dynamic distribution of nanovaccines in vivo. The targeting activation of STING pathway can enhance radiotherapy\u2010induced immune responses for inhibiting local and distant tumors, and resisting tumor metastasis. 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