Zhusheng Huang1, Yuxiang Wang1, Dan Yao1, Jinhui Wu1,2,3, Yiqiao Hu4,5,6, Ahu Yuan7,8,9. 1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and Medical School, and Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. 2. Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. 3. Institute of Drug R&D, Medical School of Nanjing University, Nanjing, 210093, China. 4. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and Medical School, and Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. huyiqiao@nju.edu.cn. 5. Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. huyiqiao@nju.edu.cn. 6. Institute of Drug R&D, Medical School of Nanjing University, Nanjing, 210093, China. huyiqiao@nju.edu.cn. 7. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and Medical School, and Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. yuannju@nju.edu.cn. 8. Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, 210093, China. yuannju@nju.edu.cn. 9. Institute of Drug R&D, Medical School of Nanjing University, Nanjing, 210093, China. yuannju@nju.edu.cn.
Abstract
Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.
Radiation therapy can potentially induce immunogenic cell death, thereby priminpan>g anpan>ti-pan> class="Disease">tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.