X‐Ray‐Activated Self‐Calibrating Second Near‐Infrared Fluorescent Probes for Precision Radiosensitization Therapy in Esophageal Cancer

Abstract Radiotherapy efficacy is often limited by tumor resistance and the lack of real‐time therapeutic monitoring. To address these challenges, a multifunctional nanoplatform (DCNP@IR‐Au), integrating X‐ray‐responsived ratiometric second near‐infrared (NIR‐II) fluorescence (FL) imaging with gold nanoparticle (AuNP)‐based radiosensitization is developed. Owing to the sensitization antenna effect of IR808, the fluorescence intensity of DCNP, which can be significantly enhanced when excited by an 808 nm laser, becomes quenched upon the incorporation of Au NPs. The ultra‐small AuNPs of DCNP@IR‐Au generate a substantial amount of hydroxyl radicals (·OH) under X‐ray irradiation, cleaving ·OH─sensitive bonds to release AuNPs, and restoring the previously quenched FL emission. While the FL intensity excited by the 980 nm laser remains constant. This approach enables precise ratiometric NIR‐II FL imaging for quantifying X‐ray‐induced ·OH levels with a detection limit of 0.40 µM. By establishing a linear correlation between ·OH levels and tumor regression effect, an adaptive radiotherapy strategy that personalizes radiation doses based on real‐time feedback, minimizing off‐target toxicity and enhancing tumor suppression by 1.8‐fold compared to conventional radiotherapy, is established. This work bridges nanotechnology with precision radiotherapy for tumor treatment, offering a transformative image‐guided platform to address radiotherapy resistance and optimize therapeutic outcomes.