基于黑色素的免疫调节纳米混合体增强了乳腺癌小鼠模型中的抗瘤免疫反应
Kangli Guo1,2,3, Zhuolong Jiao1,2,3, Xiaoyi Zhao1,2,3
1State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
ACS nano
|June 2, 2023
概括
可生物降解的黑色素/MnO纳米混合物克服瘤微环境免疫抑制. 这些纳米混合物诱导免疫细胞死亡和树突细胞成熟,增强抗瘤免疫力和减少转移.
科学领域:
- 生物材料科学 生物材料科学
- 癌症免疫疗法癌症免疫疗法
- 纳米技术 纳米技术
背景情况:
- 自然的黑色素纳米粒子 (MNP) 可以通过免疫细胞死亡 (ICD) 诱导抗瘤免疫反应.
- 瘤微环境 (TME) 通常会抑制T细胞介导的抗瘤免疫力,限制MNP的疗效.
- 开发克服TME诱导免疫抑制的策略对于有效的癌症免疫疗法至关重要.
研究的目的:
- 为增强癌症免疫疗法设计对TME敏感的可生物降解的黑色素/MnO纳米混合物.
- 调查纳米混合体触发ICD的能力,促进树突细胞 (DC) 成熟,并逆转TME免疫抑制.
- 评估开发的纳米混合体的*in vivo*抗瘤和抗转移疗效.
主要方法:
- 黑色素/MnO纳米混合物通过生物矿物化工艺合成.
- 在近红外 (NIR) 辐射下的光热效应被用来诱导ICD和释放瘤相关抗原 (TAA).
- 评估了纳米混合体对TME的免疫调节作用,包括DC成熟和PD-L1下调. *在体内*进行了抗瘤和抗转移研究,并进行了转录组学分析.
主要成果:
- 黑色素/MnO纳米混合物在NIR照射时有效触发了ICD和TAA释放.
- 这些纳米混合物促进了DC成熟,并通过减轻缺氧和酸度来逆转TME免疫抑制,从而导致PD-L1下调.
- 尽管与MNP相比,光热杀死效率较低,但黑色素/MnO纳米混合物在体内显著增强了抗瘤和抗转移作用,证实了免疫反应的激活.
结论:
- 响应TME的黑色素/MnO纳米混合物通过克服免疫抑制,为癌症免疫治疗提供了一个有希望的策略.
- 纳米混合体诱导ICD,成熟树突细胞和调节TME的能力有助于它们增强的治疗疗效.
- 这种方法利用了黑色素/MnO纳米混合物的内在特性,用于有效的免疫调节增强的癌症治疗.
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