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针对瘤铁/火双诱导的内源铁介导的溶酶体膜通透性的编程增强

Luwen Zhu^1,2, Jiahao Hu², Xiaochuan Wu²

¹Department of General Surgery, Center for Metabolism Research, The Fourth Affiliated Hospital of School of Medicine and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, P. R. China.

Nature communications

|March 28, 2025

概括

这项研究引入了一种新的纳米粒子,可以触发铁和热,这是一种用于癌症治疗的双细胞死亡策略. 这种方法利用内源性铁来增强瘤细胞死亡和免疫反应.

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:

铁和热是受调节的细胞死亡途径,具有对抗抗性瘤的潜力.
诱导溶酶体膜通透性 (LMP) 可以触发铁和热,由于共享的刺激,如铁和活性氧物种.

研究的目的:

开发一种能够对铁和热产生双重诱导的纳米粒子,用于增强瘤治疗.
调查内源性铁动员和溶酶体内在的芬顿化学机制的机制,以触发与LMP相关的细胞死亡.

主要方法:

上转化纳米粒子 (UCNPs) 的功能化与叶酸 (FA) 和克罗科纳因 (Cro).
使用UCNP-Cro/FA纳米粒子与近红外 (NIR) 光调动内源铁并诱导溶解体内的芬顿化学.
在体外和体内评估LMP,铁和热的诱导.

主要成果:

UCNP-Cro/FA纳米粒子成功地调动了细胞内铁,通过UCNP核心协调Fe3+并将其光降解为Fe2+.
对UCNP-Cro/FA纳米颗粒进行NIR处理,通过内源铁介导基生成,促进了LMP.
治疗引发了瘤细胞通过铁死和Caspase-1/GSDMD-依赖性热死死亡,增强了瘤免疫性.

结论:

一个新的UCNP-Cro/FA纳米粒子系统有效地整合了ferroptosis和pyroptosis用于瘤治疗.
该策略利用内源性铁和 lysosomal Fenton 化学物质来对细胞死亡进行时空控制.
这种方法显示出克服治疗耐药性和推进瘤免疫治疗的希望.

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