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

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.