基于细胞膜涂层的纳米复合材料的癌症免疫疗法 增强cGAS/STING激活通过细胞结核 阻断
Zhian Chen1, Zhenhao Li1, Huilin Huang1
1Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, P. R. China.
Small (Weinheim an der Bergstrasse, Germany)
|June 29, 2023
概括
这项研究引入了一种新的仿生纳米复合材料,通过激活cGAS/STING通路来增强癌症免疫疗法. 它克服了细胞分裂,释放瘤DNA,增强了对癌症的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 生物材料科学 生物材料科学
- 在瘤学瘤学.
背景情况:
- 这种cGAS/STING通路对天生的免疫非常重要,并有可能用于癌症免疫治疗.
- 垂死的瘤细胞的细胞分裂阻止了双链DNA (dsDNA) 的释放,导致免疫耐受性和逃生.
- 以前的研究表明,来自垂死的瘤细胞的dSDNA可以激活cGAS/STING通路.
研究的目的:
- 合成一种癌细胞膜仿生纳米复合物,以增强cGAS/STING通路并抑制血细胞分裂,以改善癌症免疫疗法.
- 研究纳米复合材料在触发化疗/化学动力学治疗和促进免疫刺激性二次亡方面的治疗作用.
主要方法:
- 一种癌细胞膜仿生纳米复合物的合成.
- 纳米复合物的内部化由癌细胞触发化疗/化学动力学治疗和DNA损伤.
- 通过使用释放的Annexin A5蛋白来促进dSDNA释放来抑制细胞形成.
- 激活cGAS/STING通路,增强树突细胞交叉呈现,以及与瘤相关的巨细胞的M1极化.
- 在体内实验以评估细胞毒性T细胞的招募,免疫记忆和与免疫检查点阻塞的组合疗法.
主要成果:
- 纳米复合物触发了化疗/化动疗,破坏了癌细胞内的核和线粒体DNA.
- 附录素A5释放抑制了效细胞分裂,并促进了二次亡,导致dSDNA的突发释放.
- 释放的dsDNA激活了cGAS/STING通路,增强了抗瘤免疫力,包括T细胞招募和M1巨细胞两极分化.
- 在体内研究表明,纳米复合材料的能力建立长期免疫记忆和增强免疫反应,当与免疫检查点封锁结合.
结论:
- 开发的仿生纳米复合材料有效地克服了细胞分裂,并增强了癌症免疫治疗的cGAS/STING通路激活.
- 这一策略通过促进dDNA释放和免疫细胞激活来促进适应性抗瘤免疫反应.
- 纳米复合材料代表了一种有前途的治疗策略,可以改善癌症免疫治疗的结果,特别是与现有治疗方法相结合时.
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