Programmed Nanosystem for Synergistic Immunogenic Cell Death Enhancing Radiotherapy‐Mediated Abscopal Effect

Abstract Abscopal effect often refers to the capability of localized radiation from X‐ray to provoke systemic anti‐tumor effects. Even radiation is able to prime anti‐cancer via adaptive immune responses, nevertheless, the abscopal effect is critically precluded by inadequate T‐cell infiltration in distant or non‐irradiated tumors. Here, a synergetic strategy is developed that is capable of substantially boosting radiation‐mediated immunogenic cell death for enhancing abscopal effect by fabricating programmed Au nanorod‐based core–shell nanoplatform with extracellular vesicles coating to simultaneously perform tumor‐specific radiotherapy sensitization. Subsequently, strong systematic immunity enhancement can be realized by the sensitized radiation potentiating immunogenic cell death and checkpoint inhibitor delivery. Distant and metastatic tumors are sufficiently inhibited via a strong abscopal effect including the strong antitumor immune responses and a long‐term immunological memory effect. The work thus engineers a unique nanoreactor strategy as a next‐generation radio‐immunotherapy approach to achieve synergistic efficacious whole‐body immune responses after local radiation, having great potential for clinical application.