金属间纳米组件增强了系统性的STING激活
金属间纳米组件增强了系统性的STING激活
作者： 小柯机器人 发布时间：2026/5/9 13:54:10
本期文章：《科学》：Online/在线发表
美国密歇根大学James J. Moon团队的最新研究探明了金属间纳米组件增强了系统性的STING激活。2026年5月7日出版的《科学》发表了这项成果。
小组报告CRYSTAL，一种结构有序的金属间纳米颗粒，用于有效的系统性STING激活。晶体自组装从锰离子插入环二核苷酸，使精确的结构控制。在超低静脉注射剂量（每公斤0.003毫克）下，CRYSTAL激活了小鼠、狗和非人灵长类动物的STING，没有细胞因子释放综合征。CRYSTAL在晚期小鼠和家兔模型中诱导小鼠肿瘤消退，重塑免疫抑制环境，促进宿主STING依赖性CD8 + T细胞启动。CRYSTAL在人头颈部鳞状细胞癌活检中激活干扰素反应，强调其在癌症免疫治疗中的转化潜力。
据介绍，自然系统主题金属离子形成有序的结构，调节生物过程，激发纳米疗法的合理设计。环鸟苷单磷酸-腺苷单磷酸合成酶干扰素基因刺激因子（cGAS-STING）途径驱动抗肿瘤免疫，但由于药理和毒性较差而难以全身激活。
附：英文原文
Title: Intermetallic nanoassemblies potentiate systemic STING activation
Author: Xingwu Zhou, Xiang Ling, Xiaoqi Sun, Ziye Wan, Tobias Dwyer, Timothy C. Moore, Quguang Li, Hannah E. Dobson, Qi Wu, Xiangbo Kong, Fang Xie, Xinran An, Jingyao Gan, Kaikai Wang, Young Seok Cho, Wang Gong, Katherine Dong, Jie Zhang, Mariko Takahashi, Cheng Xu, Swetha Kodamasimham, Jie Xu, Vilma Yuzbasiyan-Gurkan, Steven B. Chinn, Anna Schwendeman, Sharon C. Glotzer, Yu Leo Lei, James J. Moon
Issue&Volume: 2026-05-07
Abstract: Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING–dependent CD8+ T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for cancer immunotherapy.
DOI: adx1893
Source: https://www.science.org/doi/10.1126/science.adx1893