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以线粒体为目标的一氧化碳输送纳米平台,通过代谢免疫重编程来增强癌症免疫治疗

Chengbin Wang¹, Xuan Cheng², Jian Fang¹

¹Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.

Journal of controlled release : official journal of the Controlled Release Society

|November 8, 2025

概括

这项研究引入了一种新型的一氧化碳释放纳米平台,该纳米平台针对线粒体,以降低PD-L1表达的调节,增强抗瘤免疫力并克服对癌症免疫疗法的抵抗力.

科学领域:

生物医学工程生物医学工程
癌症研究癌症研究
免疫治疗是一种免疫疗法.

背景情况:

编程死亡1/编程死亡带1 (PD-1/PD-L1) 阻塞疗法显示临床有效性,但面临患者响应率和耐药性的挑战.
目前的免疫疗法需要新的策略来克服瘤微环境介导的免疫抑制.

研究的目的:

开发一种针对线粒体的,提供一氧化碳 (CO) 的纳米平台 (CMIH),以破坏PD-L1/PD-1轴.
为了增强抗瘤免疫力和克服癌症免疫治疗中的抵抗力.

主要方法:

通过在基于铜的金属有机框架内共同封装一个CO供体 (MnCOTPP) 和绿素,并进行氨酸表面修饰,设计了一个纳米平台 (CMIH).
利用近红外辐射触发线粒体局部化的CO释放,抑制细胞染色体c氧化酶,缓解瘤缺氧,并产生单片氧.
研究了CMIH的机制,包括HIF-1α下调,AMPK介导的PD-L1降解和PD-L1/PD-1轴阻塞.

主要成果:

CMIH有效抑制了细胞染色体c氧化酶,减少了瘤缺氧,并诱导了氧化应激和免疫细胞死亡.
在体内研究表明,CMIH激活了AMPK,抑制了HIF-1α和PD-L1的表达,并抑制了瘤生长和转移.
该纳米平台通过重新编程免疫抑制瘤微环境,证明了强大的抗瘤免疫力.

结论:

开发的基于CO的纳米治疗策略协同针对新陈代谢重编程和免疫检查点封锁.
CMIH提供了一种有前途的方法来解决当前癌症免疫治疗的局限性,提高患者的反应率和克服抵抗机制.

关键词:

通过AMPK介导的PD-L1降解.癌症免疫疗法癌症免疫疗法一氧化碳的一氧化碳.在HIF-1α下调调节下.以线粒体为目标的线粒体

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