Targeting STING Activation by Antigen-Inspired MnO₂ Nanovaccines Optimizes Tumor Radiotherapy

Immune checkpoint blockers therapy can improve the radiotherapy-induced immunosuppression by enhancing interferon secretion, but still suffer from low clinical response rate and potential adverse effects. Mn²⁺ -mediated 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 Mn²⁺ to innate immune cells and targeting activation of STING pathway. Herein, a novel antigen-inspired MnO₂ nanovaccine is fabricated as Mn²⁺ source and functionalized with mannose, enabling it to target innate immune cells to activate the STING pathway. Meanwhile, the release of Mn²⁺ 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-induced immune responses for inhibiting local and distant tumors, and resisting tumor metastasis. The study proposes an optimized radiotherapy strategy through targeting STING activation of antigen-inspired nanovaccines.