One‐Pot Synthesis of Oxygen Vacancy‐Rich Amorphous/Crystalline Heterophase CaWO₄ Nanoparticles for Enhanced Radiodynamic‐Immunotherapy

Abstract Radiodynamic therapy that employs X‐rays to trigger localized reactive oxygen species (ROS) generation can tackle the tissue penetration issue of phototherapy. Although calcium tungstate (CaWO₄) shows great potential as a radiodynamic agent benefiting from its strong X‐ray absorption and the ability to generate electron–hole (e⁻‐h⁺) pairs, slow charge carrier transfer and fast e⁻‐h⁺ recombination greatly limit its ROS‐generating performance. Herein, via a one‐pot wet‐chemical method, oxygen vacancy‐rich amorphous/crystalline heterophase CaWO₄ nanoparticles (Ov‐a/c‐CaWO₄ NPs) with enhanced radiodynamic effect are synthesized for radiodynamic‐immunotherapy of cancer. The phase composition and oxygen vacancy content of CaWO₄ can be easily tuned by adjusting the solvothermal temperature. More intriguingly, the amorphous/crystalline interfaces and abundant oxygen vacancies accelerate charge carrier transfer and suppress e⁻‐h⁺ recombination, respectively, enabling synergistically improved ROS production from X‐ray‐irradiated Ov‐a/c‐CaWO₄ NPs. In addition to directly inducing oxidative damage of cancer cells, radiodynamic generation of ROS also boosts immunogenic cell death to provoke a systemic antitumor immune response, thereby allowing the inhibition of both primary and distant tumors as well as cancer metastasis. This study establishes a synergistic enhancement strategy involving the integration of phase and defect engineering to improve the ROS generation capacity of radiodynamic‐immunotherapeutic anticancer nanoagents.