STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses  

作　　者：Taokun Luo Xiaomin Jiang Yingjie Fan Eric Yuan Jinhong Li Langston Tillman Wenbin Lin 

机构地区：[1]Department of Chemistry,University of Chicago,Chicago 60637,USA [2]Department of Radiation and Cellular Oncology and the Ludwig Center for Metastasis Research,University of Chicago,Chicago 60637,USA

出　　处：《National Science Review》2024年第7期183-198,共16页国家科学评论（英文版）

基　　金：funding from the National Cancer Institute(1R01CA253655);the University of Chicago Medicine Comprehensive Cancer Center(NIH CCSG:P30 CA014599).

摘　　要：Radiotherapy is widely used for cancer treatment,but its clinical utility is limited by radioresistance and its inability to target metastases.Nanoscale metal-organic frameworks(MOFs)have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment.We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy.Herein,we develop a robust nanoradiosensitizer,GA-MOF,by conjugating a STING agonist,2′,3′-cyclic guanosine monophosphate–adenosine monophosphate(GA),on MOFs for synergistic radiosensitization and STING activation.GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures)and transforming them into immunostimulatory hotspots with radiotherapy.Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation.Our work not only demonstrates the potent radiosensitization of GA-MOF,but also provides detailed mechanisms regarding MOF distribution,immune regulatory pathways and long-term immune effects.

关 键 词：metal-organic framework RADIOSENSITIZATION STING agonist artificial leukocytoid structures immune hotspots immunotherapy nanomedicine 

分 类 号：TB383.1[一般工业技术—材料科学与工程]