X‐Ray‐Responsive Zeolitic Imidazolate Framework‐Capped Nanotherapeutics for Cervical Cancer‐Targeting Radiosensitization

Abstract Developing radiosensitizers based on the characteristics of the tumor microenvironment can improve the effectiveness and overcome the bottleneck of cervical cancer radiotherapy. Herein, an in situ synthesis strategy is demonstrated by using a highly bioactive zeolitic imidazolate framework to cap Mn₃O₄ and folic acid as targeting molecules (FA‐Mn₃O₄@ZIF‐8) to achieve enhanced radiosensitization against cervical cancer. As expected, the ZIF‐8 cap on the surface of Mn₃O₄ responds more effectively to X‐rays. Meanwhile, by facilitating the presence of oxygen vacancies and valence transition of manganese on the surface of Mn₃O₄, the ZIF‐8 cap on Mn₃O₄ can increase the catalytic capacity for hydrogen peroxide (H₂O₂) and glutathione as well as produce more singlet oxygen under X‐ray, alleviate hypoxia within the tumor microenvironment, and increase reactive oxygen species production. Moreover, FA‐Mn₃O₄@ZIF‐8 shows excellent radiotherapy‐sensitizing properties in vitro and in vivo by promoting DNA damage and apoptosis. Collectively, this study suggests that designing and construction of X‐ray responsive nanoradiosensitizers could be a good way for future clinical radiotherapy of malignant cervical cancer.