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线粒体向的布雷基纳脂质体促进了线粒体相关的铁亡,用于促进在膀癌中检查点阻塞免疫治疗

Qiubo Ding¹, Weinan Tang¹, Xianglong Li²

¹Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology, Nanjing University, Nanjing 21008, China.

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

|September 17, 2023

概括

检查点阻断免疫疗法 (CBI) 在癌症治疗方面表现有前途. 一种新型的线粒体向性脂质体,载有布雷奎纳 (BQR@MLipo),增强铁亡,通过促进T细胞透,提高CBI在膀癌中的有效性.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
纳米医学是一种纳米医学.

背景情况:

检查点阻塞免疫疗法 (CBI) 提供了显著的癌症治疗益处.
CBI的低响应性限制了其在膀癌治疗中的有效性.
铁灭诱导可以通过触发免疫细胞死亡 (ICD) 来增强CBI反应能力.

研究的目的:

开发一种带有布雷奎纳 (BQR@MLipo) 的线粒体向性脂质体,以增强膀癌中的铁亡.
调查BQR@MLipo诱导铁和免疫反应的机制.
评估BQR@MLipo与CBI结合在体内治疗膀癌的疗效.

主要方法:

合成了载有布雷奎纳 (BQR@MLipo) 的线粒体向性脂质体.
在体外研究评估了BQR@MLipo对膀癌细胞的影响,包括线粒体积累,DHODH抑制,脂质过氧化,ROS产生和DAMPs释放.
在体内研究评估了BQR@MLipo的瘤积累,免疫细胞透 (CD8+ T细胞) 和在膀癌模型中的抗瘤疗效,与CBI结合.

主要成果:

BQR@MLipo在线粒体中选择性积累,抑制DHODH并通过脂质过氧化和ROS诱导铁.
铁灭引发了损伤相关分子模式 (DAMP) 的释放,并激活了cGAS-STING通路,促进了抗瘤免疫力.
在体内,BQR@MLipo增强了CD8+ T细胞透到瘤微环境中,与CBI相结合时导致膀瘤生长的显著抑制.

结论:

线粒体向的布雷奎纳脂质体 (BQR@MLipo) 在膀癌细胞中有效诱导铁亡.
BQR@MLipo通过促进DAMP的释放和激活cGAS-STING通路来增强抗瘤免疫反应.
BQR@MLipo是一个有前途的治疗策略,可以提高检查点阻塞免疫治疗膀癌的疗效.

关键词:

布雷奎纳尔 (Brequinar) 的意思检查点封锁免疫疗法铁化是铁化的一种.脂质细胞体中的脂肪体.线粒体向的目标是线粒体

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