Systemic Immunity Triggered by Boron Neutron Capture Therapy via Manganese-Borate Complex

Conventional radiotherapy compromises antitumor immunity through collateral damage to immune cells. While boron neutron capture therapy (BNCT) enables tumor-selective ¹⁰B (n, α) ⁷Li reactions, clinical agents like boronophenylalanine (BPA) suffer from excessive dosing and exhibit immune-metabolic inertia. We report a biomineralized albumin-based BNCT agent (Albumin@MnB) synthesized from clinically accessible borax, manganese, and albumin, which unlocks neutron capture-triggered immunotherapeutic activation. Albumin@MnB achieves potent tumor suppression at reduced boron doses, demonstrating superior efficacy compared with BPA. Importantly, Albumin@MnB enhances intratumoral immune cell infiltration and suppresses distant tumor growth, synergizing with adoptive T cell immunotherapy and immune checkpoint inhibitors. By integrating tumor-specific radiolytic energy deposition with metabolic reprogramming and immune activation, this strategy establishes boron neutron capture immunotherapy (BNCI) as a multimodal therapeutic paradigm that bridges targeted radiolysis with systemic antitumor immunity.