An MRI-visible nanotheranostic establishes a self-amplifying pyroptosis-STING-IFN-β circuit for CD8⁺ T cell...

Effective cancer immunotherapy relies on robust infiltration and sustained functionality of tumor-resident cytotoxic CD8⁺ T cells. Here we report a magnetic resonance imaging (MRI)-visible nanotheranostic that integrates redox modulation, inflammatory cell death, and innate immune sensitization to establish a self-amplifying pyroptosis-STING-IFN-β circuit for CD8⁺ T cell immunoactivation. The nanotheranostic is constructed through manganese ion (Mn²⁺)-catalyzed oxidative polymerization of polyphenols, enabling engineered reactive oxygen species (ROS) generation and localized metal ion availability. Functionally, intracellular ROS triggers caspase-3-dependent gasdermin E (GSDME) cleavage and pyroptosis, while concomitant mitochondrial perturbation increases cytosolic mitochondrial DNA (mtDNA) and sensitizes the cGAS-STING pathway to Mn²⁺-enhanced activation, resulting in IFN-β production. IFN-β further reinforces dendritic cells maturation and CD8⁺ T cells priming, whereas inflammatory pyroptosis amplifies mtDNA availability, together forming a self-amplifying positive-feedback circuit that magnifies antitumor immunity. In vivo, this coordinated mechanism promotes effective CD8⁺ T cells infiltration and memory formation. Owing to its high longitudinal relaxivity, the nanotheranostic enables clear T₁-weighted MRI contrast with pronounced tumor accumulation and prolonged retention, supporting imaging-guided immunotherapy. This work presents a functional materials strategy that couples mechanistic immune amplification with diagnostic imaging, offering a conceptual framework for translatable immunotheranostics.