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向的细胞内铜储库增强肝癌免疫疗法

Tianao Xie^1,2,3, Yukai Shan^1,2,3, Win Topatana^1,2,3

¹Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, P. R. China.

Small (Weinheim an der Bergstrasse, Germany)

|July 21, 2025

概括

肝细胞癌是一种"冷瘤",可以通过重新编程其免疫微环境来治疗. 声波可激活纳米粒子触发cuproptosis和免疫细胞死亡,增强免疫治疗的有效性.

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:

肝细胞癌 (HCC) 是一种具有低免疫原性的"冷瘤",导致对常规免疫疗法的反应不佳.
调节瘤免疫微环境 (TIME) 对于提高癌症治疗疗效至关重要.

研究的目的:

开发可激活纳米颗粒 (STCN),诱导内源性cuproptosis,用于增强HCC的免疫疗法.
研究STCN在重编程TIME和增强抗癌免疫反应方面的潜力.

主要方法:

制造N,N,N',N'-tetrakis ((2-pyridinylmethyl) -1,2-ethanediamine (TPEN) 封装的针对癌症的纳米粒子 (STCN).
超声波照射触发TPEN释放,铜化,以及随后的反应性氧物种 (ROS) 生成.
在HCC模型中对cuproptosis诱导,免疫细胞死亡 (ICD) 和T淋巴细胞透的评估.
在体内对抗编程细胞死亡蛋白1 (PD1) 进行组合疗法的评估.

主要成果:

通过叶酸介导的内细胞化,STCN被HCC细胞有效地内化.
超声波触发的TPEN释放启动了导致cuproptosis,ROS生产和ICD的级联.
与抗PD1治疗相结合的STCNs在体内和其他固体瘤模型中显示出显著的抗瘤疗效.

结论:

通过STCNs内源性cuproptosis免疫促进是一种可行的策略,以克服"冷瘤"的挑战.
这种方法有效地重新编程瘤免疫微环境,提高免疫疗法结果.
开发的策略对各种固体瘤具有广泛的治疗潜力,为癌症治疗提供了一个有希望的新途径.

关键词:

这就是cuproptosis.肝细胞癌是肝细胞癌.免疫性细胞死亡免疫性细胞死亡金属有机框架的框架.声动力学疗法声动力学疗法

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