协同的ROS生成和内源性的方向过载诱导活细胞中的线粒体功能障碍
Fengying Shao1, Jianyu Han2, Zhaoyan Tian3
1Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, State Key Laboratory of Digital Medical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
Biomaterials
|August 24, 2023
概括
这项研究介绍了一种用于癌症治疗的新型纳米平台,该纳米平台可以将细胞内 (Ca2+) 从细胞内网膜导向线粒体. 这种有针对性的过载增强了线粒体功能障碍,以有效抑制瘤.
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:
- 线粒体功能障碍是癌症治疗的关键目标.
- 提升线内线粒体内 (Ca2+) 是一个有前途的策略,但目前的方法在Ca2+运输控制和选择性方面面临挑战.
- 以内源性Ca2+有效地过载线粒体仍然是一个重大障碍.
研究的目的:
- 为增强线粒体Ca2+吸收开发一个细胞内Ca2+定向运输通道.
- 创建一个纳米平台,从内分泌网膜 (ER) 到线粒体进行选择性Ca2+输送.
- 研究反应性氧物种 (ROS) 生成和线粒体Ca2+过载对瘤抑制的协同效应.
主要方法:
- 一个级联释放纳米平台的制造:ABT-199@脂质体/多克索鲁@FeIII-酸 (ABT@Lip/DOX@Fe-TA).
- 利用瘤酸性微环境释放Fe3+并随后减少到Fe2+以产生ROS.
- 使用近红外 (NIR) 光照射触发ABT-199释放,ROS组合,并形成IP3R-Grp75-VDAC1通道用于定向的Ca2+运输.
主要成果:
- 该纳米平台成功建立了内源Ca2+从ER到线粒体的定向运输道.
- 能够显著提高线粒体内Ca2+水平的调节.
- 协同的ROS生成和线粒体Ca2+过载导致了线粒体功能障碍的加剧和有效的瘤抑制.
结论:
- 开发的纳米平台有效地克服了用于瘤治疗的内源Ca2+运输的局限性.
- 有针对性的线粒体Ca2+过载和ROS生成是癌症治疗的有效策略.
- 这项工作为内源性Ca2+参与的癌症疗法提供了一种新的方法.
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