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

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：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.

外文关键词：

metal-organic frameworkradiosensitizationSTING agonistartificial leukocytoid structuresimmune hotspotsimmunotherapynanomedicine

作者：

Taokun Luo、Xiaomin Jiang、Yingjie Fan、Eric Yuan、Jinhong Li、Langston Tillman、Wenbin Lin

展开 >

作者单位：

Department of Chemistry,University of Chicago,Chicago 60637,USA

Department of Radiation and Cellular Oncology and the Ludwig Center for Metastasis Research,University of Chicago,Chicago 60637,USA

基金：

National Cancer InstituteUniversity of Chicago Medicine Comprehensive Cancer Center

项目编号：

1R01CA253655NIH CCSG:P30 CA014599

出版年：

2024

DOI：

10.1093/nsr/nwae167

国家科学评论(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.11(7)