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超分子循环二核酸纳米颗粒用于STING介导的癌症免疫疗法

Li Xu^1,2,3, Hongping Deng², Liang Wu¹

¹School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

|May 30, 2023

概括

研究人员使用内源分子开发了新的循环二核酸纳米颗粒 (CDG-NP),以增强癌症免疫治疗的STING激活. 这些纳米粒子改善药物输送,增强抗瘤免疫力,并克服传统循环二核酸的挑战.

科学领域:

纳米技术纳米技术
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

干扰素基因刺激器 (STING) 激活可以重新编程瘤微环境 (TME),以启动抗瘤免疫力.
循环二核酸 (CDN) 的临床转化,天然的STING激动剂,受到稳定性差,半衰期短,膜透性低的限制.

研究的目的:

开发一种用于循环二核酸 (CDN) 的新型纳米输送系统,以增强STING介导的癌症免疫疗法.
使用内源性小分子创建稳定的循环二核酸纳米粒子 (CDG-NP),以提高输送和有效性.

主要方法:

使用油酸和脱氧胺构建了一个疏水性核酸脂质 (3',5'-diOA-dC).
通过超分子力组装的CDG-NP (平均直径59.0±13.0nm).
在黑色素瘤携带的小鼠中通过内和全身注射评估了CDG-NP.

主要成果:

与自由CDG相比,CDG-NPs在瘤部位显示了CDG的增强保留和细胞内输送.
CDG-NPs显著提高了STING激活和TME免疫性.
在临床前黑色素瘤模型中增强了STING介导的抗瘤免疫力.

结论:

一个灵活的超分子纳米传送系统CDN使用内源的小分子成功开发.
CDG-NPs代表了STING介导的癌症免疫治疗的有希望的平台,克服了免费CDN的局限性.

关键词:

癌症免疫疗法癌症免疫疗法循环性二核酸是循环性的二核酸.刺痛是一种刺痛.超分子纳米药物输送系统瘤微环境重新编程

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