Gadolinium Neutron Capture Reaction-Induced Nucleodynamic Therapy Potentiates Antitumor Immunity  

作　　者：Dongban Duan Yi Han Zhiyu Tu Haoxuan Guo Zizhu Zhang Yaxin Shi Jiyuan Li Qi Sun Junyi Chen Zhu Li Tong Liu Daqing Cui Zhibo Liu 

机构地区：[1]Beijing National Laboratory for Molecular Sciences,Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science,NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals,Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871 [2]Department of Radiochemistry,China Institute of Atomic Energy,Beijing 102413 [3]Department of Nuclear Science and Technology,School of Energy and Power Engineering,Xi’an Jiaotong University,Xi’an 710049 [4]Beijing Nuclear Industry Hospital,Beijing 100045 [5]Peking University–Tsinghua University Center for Life Sciences,Peking University,Beijing 100871 [6]Key Laboratory of Carcinogenesis and Translational Research,Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing [7]Beijing Capture Tech Co.Ltd.,Beijing 102413 [8]Department of Materials and Environmental Chemistry,Stockholm University,Stockholm SE-10691 [9]Changping Laboratory,Beijing 102206

出　　处：《CCS Chemistry》2023年第11期2589-2602,共14页中国化学会会刊（英文）

基　　金：funded by the Ministry of Science and Technology of the People’s Republic of China(Grant No.2021YFA1601400);the Central Guidance for Local Science and Technology Development Projects(No.202138-03);the National Nature Science Foundation of China(Grant No.U1867209);the Beijing Municipal Natural Science Foundation(Grant No.Z200018);Changping Laboratory under the project number(2021C-07-01);the Special Foundation of Beijing Municipal Education Commission(Grant No.3500-12020123);Li Ge-Zhao Ning Life Science Youth Research Foundation(LGZNQN202004)to Z.L.We thank the facility support from the Analytical Instrumentation Center of Peking University.

摘　　要：A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect.Gadolinium neutron capture therapy(GdNCT)is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations(e.g.,Auger electrons,γ-rays,etc.)in cancer cells when^(157Gd)is irradiated with thermal neutrons.Yet,its clinical application has been postponed due to the poor ability of Auger electrons andγ-rays to kill cells.Here,we engineered a^(157Gd)-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both•OH and immunogenic 1O2 in cancer cells,thereby provoking a strong antitumor immune response.This study unveils the fact and mechanism that NDT heats tumor immunity.Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectlymatches the size of nanomaterials.Inmouse tumormodels,NDT causes nearly complete regression of both primary and distant tumor grafts.Thus,this^(157Gd)-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy;its applicationmay expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases,which are responsible for 90%of all cancer deaths.

关 键 词：neutron capture therapy RADIOCHEMISTRY RADIOTHERAPY IMMUNOTHERAPY 

分 类 号：R730.3[医药卫生—肿瘤]