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Long-term monitoring of tumor-related autophagy in vivo by Fe3O4NO· nanoparticles
Biomaterials ( IF 14.0 ) Pub Date : 2018-07-04 , DOI: 10.1016/j.biomaterials.2018.07.004
Chao Zhang , Jing Ren , Jian He , Yin Ding , Da Huo , Yong Hu

In vivo read-out of autophagy is of great therapeutic and fundamental significance, and yet being conducted exclusively in high cost transgenic animal models. As an attempt to readily monitor the autophagy flux, we herein proposed an autophagy-responsive magnetic resonance imaging based on radical-conjugated magnetic nanoparticles. In principle, both the NO· radical and Fe3O4 nanoparticles are stable, and separately contributing to an observation of enhanced T1-and T2-weighted imaging, respectively. Meanwhile, the onset of autophagy concomitantly simulates the mass production of reactive species, and consequently quenches the T1-signal of NO·. On this basis, the content of autophagy flux is reflected by the ratio of T1-signal intensity to that of T2-signal, which is condition-insensitive, as a function of time. Assisted with such strategy, an unprecedented protection role autophagy played in respond to heat stress has been revealed, through which the killing effect of magneto-hyperthermia was greatly impeded. Furthermore, we noticed that the impairment of autophagy through the sequential chemotherapy, can markedly improve the therapeutic outcome, in a manner monitored and thoroughly analyzed using the strategy reported herein. We therefore believe that such a study offers a feasible method for in vivo read-out of autophagy and gives us insights how autophagy influences the therapeutic index of cancer treatments.



中文翻译:

Fe 3 O 4 NO·纳米粒子对体内肿瘤相关自噬的长期监测

体内自噬的读出具有重要的治疗和根本意义,并且仅在高成本的转基因动物模型中进行。为了容易地监测自噬通量,我们在本文中提出了基于自由基共轭磁性纳米粒子的自噬响应磁共振成像。原则上,NO·自由基和Fe 3 O 4纳米粒子都是稳定的,并且分别有助于观察增强的T 1T 2加权成像。同时,自噬的发生同时模拟了反应性物质的大量产生,因此淬灭了T 1。-NO·的信号。在此基础上,自噬通量的含量通过T 1-信号强度与T 2-信号的比率(时间无关)来反映,该比率对时间不敏感。在这种策略的辅助下,揭示了自噬对热应激起的前所未有的保护作用,从而极大地阻碍了磁热疗的杀伤作用。此外,我们注意到通过使用本文报道的策略监测和彻底分析的方式,通过顺序化疗对自噬的损害可以显着改善治疗效果。因此,我们认为这样的研究为体内提供了一种可行的方法。 读取自噬,并为我们提供见解,了解自噬如何影响癌症治疗的治疗指数。

更新日期:2018-07-05
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