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线粒体向的多功能纳米颗粒结合了cuproptosis和编程细胞死亡-1下调用于癌症免疫疗法

Youyou Li¹, Jing Liu^1,2, Ralph R Weichselbaum²

¹Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|July 16, 2024

概括

这项研究引入了Cu/TI纳米颗粒,可以输送铜离子并抑制PD-L1,有效诱导癌细胞死亡并增强小鼠模型中的抗瘤免疫力.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症研究癌症研究

背景情况:

质和免疫检查点抑制在癌症治疗方面表现有前途.
将铜离子和抑制剂同时有效地输送到瘤是具有挑战性的.

研究的目的:

开发一种针对线粒体的纳米级协调聚合物颗粒 (Cu/TI),用于有效诱导杯亡和PD-L1下调.
在临床前癌症模型中评估Cu/TI在抑制瘤进展方面的疗效.

主要方法:

合成了一种纳米级协调聚合物颗粒 (Cu/TI),其中包括Cu(II) 和5-碳基-8-基 (TI) 的三联体.
在大肠直肠癌和三阴性乳腺癌的小鼠模型中系统地施用Cu/TI.
评估瘤积累,诱导质亡,PD-L1表达,T细胞透和激活以及瘤进展.

主要成果:

在瘤组织中有效积累的Cu/TI.
Cu/TI有效诱导了免疫性癌细胞死亡,并降低了PD-L1的表达.
Cu/TI促进了细胞毒性T淋巴细胞的透和激活,显著抑制了瘤的进展,没有明显的副作用.

结论:

针对线粒体的Cu/TI纳米颗粒为联合诱导cuproptosis和抑制免疫检查点提供了一个有希望的策略.
在结直肠和三阴性乳腺癌模型中,Cu/TI显示出显著的抗瘤疗效.
这种方法有可能开发新的癌症免疫疗法.

关键词:

在PD-L1下调规则下.癌症免疫疗法免疫疗法这就是cuproptosis.针对线粒体的目标纳米医药是一种纳米医药.

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