基于铜的金属有机框架通过系统地破坏动态平衡的细胞逆位稳定来克服癌症化学阻力
Jia Liu1, Ye Yuan1,2, Yanni Cheng1
1Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Journal of the American Chemical Society
|February 22, 2022
概括
一种基于铜的新型金属有机框架 (CuHPT) 通过破坏它们的氧化还原平衡来向耐药癌细胞,诱导氧化应激并选择性杀死癌细胞. 这种方法在临床前模型中显示出克服化疗抵抗的巨大潜力.
科学领域:
- 生物医学工程
- 材料科学
- 癌症学
背景情况:
- 化学药物耐药性是癌症复发的主要驱动因素,通常由复杂的细胞机制加剧.
- 常规疗法对抗性癌症经常失败, 有时甚至通过其他途径促进抗性.
研究的目的:
- 设计一种针对抗药性癌细胞独特的生物化学弱点的新疗法.
- 研究一种基于铜的金属有机框架 (CuHPT) 克服化药耐药性的潜力.
主要方法:
- 开发一个纳米铜/基金属有机框架 (CuHPT).
- 通过谷氨 (GSH) 触发的CuHPT在癌细胞中的分解机制的研究.
- 通过ROS生成和GSH耗尽诱导氧化应激的CuHPT的能力.
- 在体外和体外对抗药性癌细胞的CuHPT细胞毒性抑制的评估.
主要成果:
- 在耐药细胞中,CuHPT可选择性地分解,释放铜离子和甲基醇配体.
- 通过耗尽GSH,使细胞内活性氧物种 (ROS) 的产生放大,从而导致氧化应激.
- 对多种耐药癌细胞系表现出强烈和选择性的细胞毒性.
- 在体内研究显示,CuHPT有效抑制瘤生长,并显著改善小鼠的存活率.
结论:
- 通过精确地解构抗药癌细胞的氧化还原稳定性,
- 这种基于铜的新型MOF为克服化学抵抗和改善癌症治疗结果提供了有希望的策略.
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