Soft X-ray-Enhanced Reactive Oxygen Species Generation in Mesoporous Titanium Peroxide and the Application in Tumor Synergistic Therapy

Mesoporous titanium peroxide TiOx nanospheres with a high surface area are synthesized for the application of an advanced drug system. The mesoporous TiOx nanospheres have a high specific surface area of 681.89 m2/g and suitable pore size (∼3 nm) that can effectively upload doxorubicin (DOX) and possesses a high drug storage capacity of 146.08%. They show a distinct ability to produce reactive oxygen species (ROS) in response to X-ray irradiation, which can effectively improve the radiotherapy in tumor treatment using the lung cancer cell line. The ROS generation of TiOx is more than ten-fold higher than that of TiO2. No apparent toxicity is found for the TiOx material itself without X-ray irradiation. In vitro and in vivo experiments show that TiOx/DOX nanodrugs significantly enhance cytotoxicity in response to X-ray irradiation. CCK8 assays display that the TiOx/DOX nanodrug has higher cancer treatment efficiency in response to X-ray irradiation because of the synergistic effect of chemotherapy and generation of ROS. In the in vivo experiments using lung cancer tumor-bearing mice model, the tumor inhibition rate in the TiOx/DOX + X-ray group increased by 90.4% compared to the untreated control group, showing a good synergistic chemo-radiotherapy effect in tumor treatment.