通过基因干扰和活性氧物种放大促进癌症治疗的内源铁介导铁化
Sen Li1, Wentao Wang2, Shixu Kou3
1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China; Department of Oncology, Wuxi People's Hospital, Wuxi 214023, China; School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China.
Journal of colloid and interface science
|December 21, 2025
概括
这项研究介绍了一种新的纳米平台,它使用人体自身的铁,通过铁灭 (依赖铁的细胞死亡) 触发癌细胞死亡. 这种方法可以增强瘤抑制,同时最大限度地降低毒性.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 铁,一种依赖于铁的细胞死亡,对癌症治疗有希望.
- 目前用于诱导铁灭的铁输送方法面临毒性和耐药性问题.
- 需要一种新的策略,通过向内源性铁和抗氧化剂防御来促进铁亡.
研究的目的:
- 开发一个空间控制的纳米平台,用于在癌症治疗中增强铁灭诱导.
- 为了调动细胞内铁和拆除抗氧化物障碍,以放大ferroptotic损伤.
- 为了建立一个多功能范式,以有效和耐受性良好的ferroptosis基于癌症治疗.
主要方法:
- 构建了一个对谷氨 (GSH) 敏感的,二硫化物桥接的金属有机框架 (MOF),共同封装碳酸酶IX (CA9) 向的siRNA (siCA9) 和e6 (Ce6).
- 该纳米平台 (MOF-siCA9-Ce6) 旨在在富含GSH的瘤细胞内部化后释放有效载荷.
- 使用siCA9倒置来酸化细胞质,调动内源Fe2+,而激光激活Ce6则产生反应性氧物种 (ROS).
主要成果:
- 纳米平台成功地崩在富含GSH的细胞中,释放siCA9和Ce6并消耗GSH以增加氧化应激.
- siCA9的淘汰导致细胞酸酸化和内源Fe2+的调动.
- 激光激活的Ce6产生ROS,侵蚀脂质修复系统并驱动脂质过氧化.
- 结合的Fe2+/ROS激增抑制了关键的铁灭菌抑制剂,导致强烈的铁灭菌和显著的瘤抑制在体外和体内.
结论:
- 开发的GSH/激光激活MOF-siCA9-Ce6纳米平台有效诱导内源铁驱动的ROS增强型铁亡.
- 这种策略克服了外源铁输送的局限性,为癌症治疗提供了耐受性良好和有效的方法.
- 纳米平台为推进基于铁灭的癌症治疗建立了一个多功能范式.
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