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

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 Mn2⁺ 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.