机构:[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深圳市中医院深圳医学信息中心[5]Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China南方医科大学珠江医院[6]Department of Endodontics, Southern Medical University-Shenzhen Stomatology Hospital (Pingshan), Shenzhen, 518118, China南方医科大学深圳医院深圳市康宁医院深圳医学信息中心
The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immunerelated 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 MRIguided 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.
基金:
National Natural Science Foundation of China [82103404]; Southern Medical University Excellent Youth Scholars Training Program [2020YQPY008]; Stomatological Hospital of Southern Medical University Startup Funds [PY2020001, PY2019026]; Natural Science Foundation of Guang dong Province [2023A1515011604]; Fundamental Research Funds for the Central Universities [2022ZYGXZR042]; High-level Hospital Construction Project [KJ012019100]
第一作者机构:[1]Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, China
共同第一作者:
通讯作者:
通讯机构:[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[*1]Stomatological Hospital, Southern Medical University, No 366, Jiangnan Road, Haizhu Region, Guangzhou, 510280, China.[*2]Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, No 253 Gongye Avenue, Haizhu District, Guangzhou City, 510280, China.[*3]Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No 52 Sanlihe Road, Xicheng District, Beijing City, 100190, China[*4]Medical Research Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou City, 510080, China
推荐引用方式(GB/T 7714):
Cui Hao,Zhao Yu-Yue,Wu Qiong,et al.Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy[J].Bioactive Materials.2024,33:532-544.doi:10.1016/j.bioactmat.2023.11.010.
APA:
Cui, Hao,Zhao, Yu-Yue,Wu, Qiong,You, Yan,Lan, Zhou...&Yu, Guang-Tao.(2024).Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.Bioactive Materials,33,
MLA:
Cui, Hao,et al."Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy".Bioactive Materials 33.(2024):532-544