Bioactivated Nanoionizers: Calcium Storm‐Triggered Pyroptotic Cascade Activation Empowering Boron Neutron Capture Therapy

Abstract Boron neutron capture therapy (BNCT) is an advanced binary‐targeted radiotherapy for treating invasive malignant cancers. However, the efficacy of standalone BNCT is constrained by insufficient tumor accumulation of boron agents. Herein, bioactivated nanoionizers (BNI) is engineered via a double emulsion method, co‐encapsulating boron quantum dots (BQDs) and capsaicin (CAP, TRPV1 agonist) within a pH‐responsive CaCO 3 shell for combined BNCT/ion interference therapy (BNCIIT) against tumors. Upon cellular internalization, acidic tumor microenvironments trigger CaCO 3 dissolution, releasing penetration‐competent ultrasmall BQDs for homogeneous boron distribution while liberating Ca 2+ . The latter synergizes with capsaicin‐activated TRPV1 channels to provoke calcium overload, inducing pyroptosis‐driven immunogenicity. This dual‐action mechanism disrupts cellular homeostasis to potentiate BNCT radiosensitization. Crucially, the self‐reinforcing “ion‐neutron interplay” within this single biodegradable platform concurrently overcomes tumoral boron delivery barriers, surmounts inherent BNCT limitations, enhances radiosensitivity, and amplifies antitumor immunity. This strategy establishes a blueprint for integrated binary therapies in precision radiotherapy platforms.