Au-MnOx nanozyme-based multifunctional hydrogel for NIR-II laser triggered tumor radiotherapy sensitization

Radiotherapy (RT) is widely used for malignant tumors ablation in the clinic. However, redundant doses of X-rays might cause irreversible side effects in the periphery of tumor sites. To address this, the convergence of low-dose RT with a novel therapeutic method is promising. Here, a hydrogel system was created that combines nanozymes with NIR-II photothermal therapy and RT sensitization. Meteor hammer-like nanozyme Au-MnOx and agarose hydrogel were mixed to form multifunctional nanozyme hydrogel (MNH). The system experienced a reduction in MNH hardness when exposed to 1064 nm laser irradiation, allowing the release of Au-MnOx to react with H₂O₂ in the tumor microenvironment, resulting in the production of ·OH, which destroys bioactive substances and increases oxidative stress. This process also improves the effectiveness of hyperthermia in photothermal therapy (PTT). In addition, MNH-baed PTT enhances the RT sensitivity. Additionally, Au, with a high atomic number emits X-rays, leading to the generation of reactive oxygen species (ROS) through preexisting processes, which enhances radiation-induced DNA damage. Notably, the in vivo results indicated that MNH + NIR + RT could achieve a potent tumor inhibition rate with negligible side effects to normal tissues. This work paves a new avenue for novel nanozyme-based radiosensitization.