重振瘤相关巨细胞和诱导免疫细胞死亡:一种向的脂质体策略,以促进癌症免疫疗法
Cong Li1, Lihong Wang1, Zhihang Li1
1School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China.
International journal of pharmaceutics
|December 23, 2023
概括
这项研究介绍了DOX/R837@ManL,这是一种针对免疫抑制瘤微环境的新型脂质体. 它有效地将M2巨细胞转化为M1,增强瘤细胞抗原性,并提高免疫疗法的疗效,消除瘤并防止复发.
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:
- 癌症免疫疗法面临着由M2瘤相关巨细胞 (TAMs) 介导的免疫抑制性瘤微环境 (TME) 的挑战.
- 有限的瘤细胞抗原性也限制了当前癌症免疫疗法的有效性.
研究的目的:
- 开发一种有针对性的纳米药物,DOX/R837@ManL,以克服TME诱导的免疫抑制并增强癌症免疫疗法.
- 为了研究因米基莫德 (R837) 和 doxorubicin (DOX) 通过曼诺斯受体向脂质体传递的协同作用.
主要方法:
- DOX/R837@ManL脂质体是使用曼-聚乙烯甘醇 (Man-PEG) 进行的,用于曼受体1 (MRC1) 介导的向.
- 脂质体选择性地积聚在M2 TAM和瘤部位,提供R837,将M2 TAM转化为M1 TAM和DOX,诱导免疫细胞死亡 (ICD).
主要成果:
- DOX/R837@ManL通过将TAM从M2转移到M1表型,有效地重新编程了免疫抑制的TME.
- 诱导DOX的ICD增强了瘤细胞的抗原性,促进了树突细胞的成熟,激活了先天性和适应性免疫力.
- 在体内研究显示,主要瘤和肺转移的显著消除,预防术后瘤复发.
结论:
- DOX/R837@ManL通过克服TME介导的免疫抑制来证明癌症免疫疗法的有希望的策略.
- 有针对性的输送和协同作用的药物激活免疫反应,导致有效的瘤消除和长期保护.
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