铜协调驱动的纳米框架,通过抑制癌细胞干细胞的作用来有效地进行结直肠癌化学免疫治疗
Yichun Huang1, Hailong Tian2,3, Zhimin Yue2
1Department of Surgical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
Materials today. Bio
|April 16, 2025
概括
装有西斯的铜纳米框架克服了结直肠癌中的癌症干. 这种方法通过向癌症干细胞及其抵抗机制来增强化疗免疫疗法.
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:
- 癌症干细胞 (CSCs) 驱动的癌症干细胞性,显著促进结直肠癌 (CRC) 化学免疫治疗耐药性.
- 开发克服CSC介导耐药性的策略对于改善CRC治疗结果至关重要.
研究的目的:
- 重新利用铜协调驱动的金属有机纳米框架 (Cu-MOFs) 来解决与癌症干性相关的CRC中的化疗免疫疗法耐药性.
- 为了研究含有西斯的Cu-MOFs (Cu-MOF@CDDP) 在使CRC对化疗免疫疗法的敏感性方面的疗效.
主要方法:
- Cu-MOFs被加载了西斯来创建Cu-MOF@CDDP纳米粒子.
- 评估了Cu-MOF@CDDP的细胞吸收,药物/离子释放以及包括DNA损伤,cuproptosis诱导和免疫通路激活在内的作用机制.
- 评估了对干性相关蛋白质 (ZEB1,c-MYC) 和化疗免疫治疗敏感性的影响.
主要成果:
- Cu-MOF@CDDP纳米粒子被CRC细胞有效地内化,释放出西斯和铜离子 (Cu2+).
- 西斯普拉丁诱导了DNA损伤,而Cu2+触发了cuproptosis和耗尽的谷氨 (GSH).
- 这一过程激活了cGAS-STING通路,启动了抗瘤免疫力,并降低了干性标记物的调节,提高了化疗免疫疗法的疗效.
结论:
- 装载着西斯丁的重复使用的Cu-MOF显示出在克服CRC中茎性驱动的治疗耐药性的显著前景.
- 这种方法提供了一个变革性的策略,通过向癌症干系途径,使结直肠癌对化疗免疫疗法产生敏感性.
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