Xu Chen, Chen Liting, Liu Guangna, Xu Jiaqi, Lv Wei, Gao Xiaoyu, Xu Peijun, Tang Ming, Wang Yaohe, Zhao Xiao, Nie Guangjun, Cheng Keman, Liu Funan
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang 110001, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang 110001, China; Phase I Clinical Trails Center, The First Hospital of China Medical University, Shenyang 110102, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; IGDB-NCNST Joint Research Center, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang 110001, China; Phase I Clinical Trails Center, The First Hospital of China Medical University, Shenyang 110102, China.
Cell Rep Med. 2025 May 20;6(5):102078. doi: 10.1016/j.xcrm.2025.102078. Epub 2025 Apr 14.
Oncolytic viruses (OVs) combined with radiotherapy (RT) show promise but are limited by challenges such as poor intravenous delivery and insufficient RT-induced DNA damage. In this study, an oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), is developed to improve delivery, infectivity, immune response, and RT efficacy. The multifunctional polyethylenimine (PEI)-selenium-polyethylene glycol (PEG) (PSSP) enhances intravenous delivery, shields the virus from rapid clearance, and enables targeted delivery to tumor sites after RT. The exposed PEI enhances the infectivity of AD through electrostatic interactions, thereby increasing DNA damage after RT by inhibiting the expression of DNA repair proteins, such as CHEK1 and CDK1. Furthermore, AD-PEI captures and delivers RT-induced tumor-released antigens to lymph nodes, activating robust anti-tumor immune responses. Animal model data demonstrate that RadioOnco overcomes RT resistance, targets distant metastases, and promotes long-term immunity, addressing metastasis and recurrence. In summary, this intravenously injectable OV enhances RT synergy through surface modification with multifunctional materials.
溶瘤病毒（OVs）与放疗（RT）联合使用显示出前景，但受到诸如静脉内递送不佳和放疗诱导的DNA损伤不足等挑战的限制。在本研究中，开发了一种溶瘤腺病毒（AD）制剂，即放射肿瘤病毒（AD@PSSP），以改善递送、感染性、免疫反应和放疗效果。多功能聚乙烯亚胺（PEI）-硒-聚乙二醇（PEG）（PSSP）增强静脉内递送，保护病毒免于快速清除，并在放疗后实现向肿瘤部位的靶向递送。暴露的PEI通过静电相互作用增强AD的感染性，从而通过抑制DNA修复蛋白（如CHEK1和CDK1）的表达增加放疗后的DNA损伤。此外，AD-PEI捕获并将放疗诱导的肿瘤释放抗原递送至淋巴结，激活强大的抗肿瘤免疫反应。动物模型数据表明，放射肿瘤病毒克服了放疗抗性，靶向远处转移，并促进长期免疫，解决了转移和复发问题。总之，这种可静脉注射的溶瘤病毒通过用多功能材料进行表面修饰增强了放疗协同作用。
