Atorvastatin‐Loaded Mineralized Vaccine Reprograms Endosomal Trafficking to Amplify STING‐Driven Cancer Immunotherapy

Abstract

Abstract Dendritic cell (DC)‐targeted nanovaccines offer great promise for cancer immunotherapy but are severely limited by premature lysosomal degradation of antigens, which reduces cross‐presentation efficacy. Here, we report a facile yet effective biomineralization strategy to construct nanovaccine (OVA‐ATV@MnO₂) that co‐delivers ovalbumin (OVA) and atorvastatin (ATV) within MnO₂ matrix. The ATV‐mediated nanovaccine reprograms endosomal trafficking by inhibiting the mevalonate (MVA) pathway, thereby delaying endosomal maturation and preventing antigen diversion to degradative lysosomes. This intervention significantly enhances antigen preservation and MHC‐I presentation in DCs. Simultaneously, the MnO₂ framework not only stabilizes the vaccine nanostructure but also releases Mn 2 ⁺ ions as an adjuvant to potently activate the cGAS‐STING pathway, amplifying DC maturation and antitumor T‐cell priming. In vivo studies demonstrate that the nanovaccine induces robust tumor regression, suppresses metastasis, and establishes durable prophylactic immunity. By synergistically rewiring intracellular antigen trafficking and amplifying STING‐mediated immune activation, this mineralized vaccine platform provides a transformative strategy for precise cancer immunotherapy.