可生物降解的紫外线聚合物覆盖的有缺陷的金属有机框架用于诱导铁致癌的癌症治疗
Minghua Zhang1, Xianxian Yao1, Jian Xu1
1State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, 220 Handan Road, Shanghai 200433, PR China.
International journal of pharmaceutics
|March 23, 2024
概括
这项研究引入了一种新型纳米平台,通过输送铁和阿托瓦斯塔丁,诱导癌细胞死亡的一种形式 - - 铁亡. 这种方法提高了抗癌疗效和生物相容性,改善了癌症治疗.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 在瘤学瘤学.
背景情况:
- 铁,一种依赖于铁的细胞死亡,通过脂质过氧化物积累来抑制瘤生长.
- 这一过程可以由铁过载和谷氨过氧化酶4 (GPX4) 失活触发.
研究的目的:
- 为癌症治疗开发一种可生物降解的zwitterionic聚合物覆盖的阿托瓦斯塔丁 (ATV) 装载的铁金属有机框架 (Fe-MOF) 纳米平台.
- 为了研究铁和ATV输送在诱导ferroptosis增强抗癌功效的协同效应.
主要方法:
- 制造配送铁离子 (Fe2+) 和ATV的Fe-MOF,覆盖在一个zwitterionic聚合物上.
- 在体外和体内研究评估纳米粒子循环时间,瘤积累和细胞反应.
- 评估Fe-MOF在癌细胞中的崩,导致GSH耗尽,ATV和Fe2+释放,GPX4减弱和芬顿反应诱导的活性氧物种产生.
主要成果:
- 纳米平台证明了延长循环时间和增强瘤积累.
- 癌细胞内的Fe-MOF崩导致谷氨酸 (GSH) 枯竭和ATV和Fe2+的释放.
- ATV减弱了GSH和GPX4,而Fe2+触发了芬顿反应,导致致命的脂质过氧化物积累和癌细胞死亡.
结论:
- 开发的诱导铁灭的纳米平台表现出增强的抗癌疗效和有利的生物相容性.
- 这种方法为有效的抗癌疗法提供了一种可行和有前途的策略.
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