靶向线粒体的纳米颗粒放射致敏

Jun Xue, Dida Duosiken, S. Zhong, Jiao-Jiao Cao, Liang-Yun Hu, Kang Sun, Ke Tao, Sijian Pan
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引用次数: 0

摘要

为了减少高剂量辐射的副作用,人们迫切需要增敏放射治疗(RT),而具有高原子序数元素的纳米颗粒提供了一种很有前途的工具。然而,利用纳米颗粒与癌细胞之间的相互作用的知识不足阻碍了治疗结果的改善。本文采用NaGdF4:Yb,Er纳米晶体作为增敏剂,分别或联合用肿瘤靶向剂和线粒体靶向片段对其进行修饰,实现不同程度的线粒体积累。我们观察到NaGdF4:Yb,Er纳米晶体,即使没有靶向配体修饰,也能有效地进行放射增敏。此外,线粒体靶向的程度是体外和体内增敏效率的原因。通过RNA测序(RNA-seq)技术,结果归因于活性氧(ROS)介导的TNF-JNK途径和细胞周期阻滞,而不是那些非靶向纳米颗粒破坏DNA。我们的研究表明,辐射产生的ROS可以通过激活线粒体靶向纳米颗粒的替代凋亡途径来利用,因此可能提出了一种增强放射致敏的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Radiosensitization With Nanoparticles Targeting to Mitochondria
Sensitizing radiation therapy (RT) for cancer is highly desired to reduce side-effect of the harsh dose of irradiation, and nanoparticles with high atomic number elements provide a promising tool. However, insufficient knowledge on utilizing the interaction between nanoparticles and cancerous cells hampers the improvement of therapeutic outcome. We herein employed NaGdF4:Yb,Er nanocrystals as the sensitizer, and modified them with a tumor targeting agent and a mitochondria targeting moiety, separately and jointly, to achieve varied extent of mitochondrial accumulation. We observed that NaGdF4:Yb,Er nanocrystal, even unmodified with targeting ligands, is effective for radiosensitization. Furthermore, the extent of mitochondrial targeting was responsible for sensitization efficiency both in vitro and in vivo. By RNA sequencing (RNA-seq) technique, the result was ascribed to the reactive oxygen species (ROS) mediated TNF-JNK pathway and cell cycle arrest, rather than breaking DNA with those untargeted nanoparticles. Our work indicated that ROS generated by the irradiation can be utilized by activating an alternative apoptotic pathway with mitochondrial targeting nanoparticles, and therefore may suggest an approach for the enhancement of radiosensitization.
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