Manganese-enriched nanoboron agent amplifies BNCT efficacy via pyroptosis-mediated immune activation and STING pathway synergy

Boron Neutron Capture Therapy (BNCT) offers selective tumor cell ablation with minimal damage to normal tissues, but its efficacy is limited by therapy-induced immunosuppression and high intratumoral H₂O₂ levels, restricting synergy with immunotherapy. Here, we report BSA-BPA-MnO₂, a tumor microenvironment-responsive, manganese-enriched nanoboron agent designed to overcome these barriers. This nanoplatform combines efficient boron delivery with Mn²⁺-driven Fenton-like catalysis and cGAS-STING pathway activation, amplifying BNCT-induced oxidative stress and inducing immunogenic pyroptosis alongside robust type I interferon signaling. This dual mechanism transforms BNCT from a local therapy into a systemic immune activator, enhancing dendritic cell maturation and CD8⁺ T cell responses. Additionally, MnO₂ enables MRI-guided BNCT, integrating diagnostics and therapeutics. Notably, the platform achieves potent tumor suppression and systemic immune activation even at subclinical boron levels, offering a promising strategy for next-generation immune-integrated BNCT, particularly against melanoma.