Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy  

作　　者：Hao Cui Yu-Yue Zhao Qiong Wu Yan You Zhou Lan Ke-Long Zou Guo-Wang Cheng Hao Chen Yan-Hua Han Yan Chen Xiang-Dong Qi Xian-Wei Meng Li-Min Ma Guang-Tao Yu 

机构地区：[1]Stomatological Hospital,School of Stomatology,Southern Medical University,Guangzhou,510280,China [2]Medical Research Center,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,510080,China [3]Laboratory of Controllable Preparation and Application of Nanomaterials,Technical Institute of Physics and Chemistry,Chinese Academy of Sciences,Beijing,100190,China [4]Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou,510405,China [5]Department of Plastic Surgery,Zhujiang Hospital,Southern Medical University,Guangzhou,510280,China [6]Department of Endodontics,Southern Medical University-Shenzhen Stomatology Hospital(Pingshan),Shenzhen,518118,China

出　　处：《Bioactive Materials》2024年第3期532-544,共13页生物活性材料（英文）

基　　金：support from National Natural Science Foundation of China[82103404];Southern Medical University Excellent Youth Scholars Training Program[2020YQPY008];Stomatological Hospital of Southern Medical University Startup Funds[No.PY2020001,PY2019026];Natural Science Foundation of Guang dong Province(2023A1515011604);The Fundamental Research Funds for the Central Universities(2022ZYGXZR042);the High-level Hospital Construction Project(KJ012019100)for financial support.

摘　　要：The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events.Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect.Herein,we designed a Gd-based metal-organic framework(Gd-MOF)nanosystem for MRI-guided thermotherapy and synergistic immunotherapy,which featured high performance in drug loading and tumor tissue penetration.The PD-1 inhibitor(aPD-1)was initially loaded in the porous Gd-MOF(Gd/M)nanosystem.Then,the phase change material(PCM)and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM(Gd/MPC).When entering the tumor microenvironment(TME),Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness,improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1.Meanwhile,Gd/MPC can be used for contrast-enhanced MRI.Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun,and ultimately leads to the apoptosis of cancer cells after treatment.In general,Gd/MPC nanosystem not only solves the problem of system side effect,but also achieves the controlled drug release via PCM,providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

关 键 词：IMMUNOTHERAPY MICROWAVE Metal-organic framework THERMOTHERAPY Cancer imaging 

分 类 号：R730.5[医药卫生—肿瘤]