Three-in-One Nanozyme for Radiosensitization of Bladder Cancer

Yang Li,1 Yuhan Zhang,1 Na Feng,2 Fan Yu,1 Bin Liu3 1Department of Gastroenterology and Hepatology, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 2Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of ChinaCorrespondence: Fan Yu; Bin Liu, Email [email protected]; [email protected]: Bladder cancer is a common malignancy of the urinary system and the development of noninvasive therapeutic methods is imperative to avoid radical cystectomy, which results in a poor quality of life for patients.Methods: In this study, ultrasmall copper–palladium nanozymes decorated with cysteamine (CPC) nanoparticles (NPs) were synthesized to enhance the efficacy of radiotherapy (RT) in treating bladder cancer. CPC NPs react with intracellular overexpressed H2O2 in the tumor microenvironment to produce large quantities of reactive oxygen species (ROS) and induce tumor cell apoptosis. Furthermore, the CPC nanozymes can generate ample oxygen within tumors by utilizing H2O2, addressing hypoxia conditions, and mitigating radioresistance. Additionally, CPC facilitates the oxidation of glutathione (GSH) into oxidized glutathione disulfide (GSSG), blocking the self-repair mechanisms of tumor cells post-treatment. Simultaneously, CPC enhances the ionization energy deposition effect on tumor cells.Results: The results demonstrate an increased level of ROS and an elevation in oxygen content at the tumor site. Importantly, tumor growth was restrained without apparent systemic toxicity during the combined treatment.Conclusion: In summary, this study highlights the potential of CPC nanozyme-mediated radiotherapy as a promising avenue for the effective treatment of bladder cancer and demonstrates its potential for future clinical applications in the synergistic therapy of bladder cancer.Keywords: bladder cancer, radiotherapy, nanozyme, tumor microenvironment, hypoxia