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复氧反应的金属有机框架纳米囊通过调节瘤代谢重编程来增强瘤化疗免疫疗法

Yuman Dong¹, Jieru Li², Yiwei Dai²

¹Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.

Materials today. Bio

|February 3, 2025

概括

新型纳米囊向瘤代谢和免疫抑制瘤微环境,以增强化疗免疫疗法的有效性,在临床前模型中显示显著的胰腺癌生长抑制.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
免疫学免疫学免疫学

背景情况:

免疫检查点封锁 (ICB) 在瘤学中表现有前途,但通常受到免疫抑制瘤微环境 (ITM) 的限制.
瘤代谢重编程对ITM有显著的贡献,阻碍了免疫治疗的有效性.

研究的目的:

开发新的瘤微环境响应纳米囊 (DNMCs) 用于联合化疗-免疫疗法.
同时调节瘤代谢和ITM以增强抗瘤免疫反应.

主要方法:

DNMCs是使用一种酸性和氧化还原敏感的金属有机框架 (MOF) 封装Doxorubicin (DOX) 和一种氨酸-2,3-二氧化酶1 (IDO1) 抑制剂 (NLG919) 来设计的.
研究了瘤微环境中DOX和NLG919的释放和活性.
在胰腺癌患者衍生器官 (PDO) 和KPC小鼠模型中评估了抗瘤疗效.

主要成果:

DNMCs有效地输送了DOX,诱导免疫细胞死亡 (ICD),以及NLG919,抑制IDO1活动并逆转ITM免疫抑制.
用DNMCs治疗导致瘤透的CD8+细胞毒性T细胞增加和调节性T细胞 (Tregs) 减少.
在PDO和小鼠模型中,DNMCs显著抑制了胰腺癌的生长.

结论:

通过向瘤代谢重编程,DNMCs代表了增强化疗免疫疗法的有希望的策略.
这种方法增强了抗瘤免疫反应,为胰腺癌和其他恶性瘤提供了潜在的治疗途径.

关键词:

免疫原性细胞死亡免疫抑制的瘤微环境金属有机框架金属有机框架瘤氨基酸代谢的代谢瘤微环境触发了瘤的微环境

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