Copper-Based Single-Atom Nanozyme System Mimicking Platelet Cells for Enhancing the Outcome of Radioimmunotherapy

Abstract

Cheng Chen,1,* Nandi Chen,2,3,* Yan Qi,1,* Meng Lyu,2 Chaoyan Wu,4,* Conghua Xie,1 Haijun Yu1 1Department of Radiation and Medical Oncology, Hubei Province Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Department of Gastrointestinal Surgery & Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of China; 3Analysis and Testing Center, Shenzhen Technology University, Shenzhen, 518118, People’s Republic of China; 4Department of Integrated Traditional Chinese Medicine and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haijun Yu; Conghua Xie, Email [email protected]; [email protected]: Radiotherapy is an indispensable part of the multidisciplinary treatment of breast cancer (BC). Due to the potential for serious side effects from ionizing radiation in the treatment of breast cancer, which can adversely affect the patient’s quality of life, the radiation dose is often limited. This limitation can result in an incomplete eradication of tumors.Methods: In this study, biomimetic copper single-atom catalysts (platelet cell membrane camouflaging, PC) were synthesized with the aim of improving the therapeutic outcomes of radiotherapy for BC. Following guidance to the tumor site facilitated by the platelet cell membrane coating, PC releases a copper single-atom nanozyme (SAzyme). This SAzyme enhances therapeutic effects by generating reactive oxygen species from H2O2 and concurrently inhibiting the self-repair mechanisms of cancer cells through the consumption of intracellular glutathione (GSH) within the tumor microenvironment. PC-augmented radiotherapy induces immunogenic cell death, which triggers an immune response to eradicate tumors.Results: With the excellent biocompatibility, PC exhibited precise tumor-targeting capabilities. Furthermore, when employed in conjunction with radiotherapy, PC showed impressive tumor elimination results through immunological activation. Remarkably, the tumor suppression rate achieved with PC-enhanced radiotherapy reached an impressive 93.6%.Conclusion: Therefore, PC presents an innovative approach for designing radiosensitizers with tumor-specific targeting capabilities, aiming to enhance the therapeutic impact of radiotherapy on BC.Keywords: platelet cell membrane, single-atom nanozyme, radiotherapy, radioimmunotherapy, breast cancer

Keywords

• platelet cell membrane
• single-atom nanozyme
• radiotherapy
• radioimmunotherapy
• breast cancer