多功能杂交外体通过激活STING通路来增强癌症化学免疫疗法
Lili Cheng1, Peng Zhang1, Yadong Liu1
1School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong, 518107, PR China.
Biomaterials
|August 2, 2023
概括
这项研究开发了混合外体,以激活干扰素基因 (cGAS/STING) 路径的循环诺单酸-诺单酸合成酶/刺激器,通过重编程瘤微环境来增强抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术 纳米技术
- 在瘤学瘤学.
背景情况:
- 免疫抑制性瘤微环境 (ITM) 阻碍了有效的癌症免疫疗法,如检查点封锁和疫苗.
- 与瘤相关的巨细胞 (TAMs) 和调节性T细胞有助于ITM,限制抗瘤免疫反应.
- 循环氨酸单酸-氨酸单酸合成酶/刺激干扰素基因 (cGAS/STING) 路径激活通过增强先天免疫力显示出癌症治疗的前景.
研究的目的:
- 为激活cGAS/STING通路设计多功能混合外体,以克服ITM.
- 增强树突细胞 (DC) 的成熟,促进细胞毒性T淋巴细胞 (CTL) 和自然杀手 (NK) 细胞的透.
- 为了实现显著的抗瘤和抗转移疗效.
主要方法:
- 通过将CD47-装饰的瘤细胞衍生的外体与M1巨细胞衍生的外体融合而设计的混合外体.
- 用DNA向剂 (SN38) 和一个STING激动剂 (MnO2) 封装的外体.
- 评估了混合外体的瘤向能力,血液循环时间,TAM偏振,cGAS/STING激活和抗瘤效应.
主要成果:
- 杂交外体 (SN/Mn@gHE) 呈现出增强的瘤向和延长的血液循环.
- SN/Mn@gHE诱导了TAMs对M1表型的两极化,释放了SN38用于DNA损伤,并通过Mn2+刺激了cGAS/STING激活.
- 观察到显著的抗瘤和抗转移疗效,促进了DC成熟和增加了CTL和NK细胞透.
结论:
- 多功能杂交外体有效地激活cGAS/STING通路并重新编程免疫抑制瘤微环境.
- 这一策略通过促进CTL和NK细胞的DC成熟和透来增强抗瘤免疫反应.
- 开发的混合外体提供了一种改善癌症免疫治疗结果的新方法.
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