美国芝加哥大学Wenbin Lin研究小组发现， STING激动剂共轭金属有机框架诱导人工类白细胞结构和免疫热点来促进全身抗肿瘤反应。这一研究成果于2024年5月10日在线发表在国际学术期刊《国家科学评论》上。

据了解，放疗被广泛应用于癌症治疗，但其临床实用性因放射抗性和无法靶向转移而受到限制。纳米级MOF作为高Z纳米放射增敏剂，有望增强放疗效果并诱导肿瘤微环境的免疫刺激调节。

附：英文原文

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

Author: Luo, Taokun, Jiang, Xiaomin, Fan, Yingjie, Yuan, Eric, Li, Jinhong, Tillman, Langston, Lin, Wenbin

Issue&Volume: 2024-05-10

Abstract: 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 developed a robust nanoradiosensitizer, GA-MOF, by conjugating a STING agonist, 2',3'-cyclic guanosine monophosphate–adenosine monophosphate (GA), on MOF 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 immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates potent radiosensitization of GA-MOF, but also provides the detailed mechanisms regarding MOF distribution, immune regulatory pathways, and long-term immune effects.

DOI: 10.1093/nsr/nwae167

Source: https://dx.doi.org/10.1093/nsr/nwae167