PO.ET08.01 · 实验与分子治疗
金纳米棒的氧化还原调控增强MOLT 4细胞的放射敏感性
Redox modulation by gold nanorods enhances radiosensitivity in MOLT 4 cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
金纳米颗粒因其独特的光学特性而日益受到关注。在不同形状的纳米颗粒中,具有非球形形状的金纳米颗粒(Au-NPs),例如金纳米棒(Au-NR),由于其易于合成和修饰,正在各种应用中受到特别关注。它们可以与不同的分子偶联,用于生物医学应用,如肿瘤成像和治疗。先前,我们已证明小尺寸的Au-NPs根据处理方式的不同具有截然不同的效应;它们可保护细胞免受X射线诱导的凋亡,同时增强由超声和氦基冷大气压等离子体诱导的凋亡。因此,本研究旨在探讨Au-NR对X射线(2.5 Gy)诱导的凋亡的影响,以及在体外MOLT 4细胞中介导的分子通路。通过观察细胞内活性氧(ROS)生成和凋亡信号通路的变化,来测定Au-NR对X射线诱导凋亡的影响。结果表明,以0.1和0.5 μg剂量的10 nm尺寸Au-NR预处理的细胞显著增强了凋亡。通过吉姆萨(Giemsa)染色观察到典型的形态学变化,显示联合处理中凋亡性细胞死亡增强。通过流式细胞术观察到,线粒体膜电位、谷胱甘肽和细胞内钙离子水平的丧失显著增强。此外,采用蛋白质印迹(western blot)分析测定caspase-3和Bcl-2家族蛋白的表达。在本研究中,我们首次证明在联合处理中,Au-NR显著增强了低剂量X射线诱导的凋亡性细胞死亡。我们的发现表明,癌症的联合治疗将成为实现显著抗癌效应的关键方法。
查看英文原文 English abstract
Gold nanoparticles have gained increasing interest because of their unique optical properties. Among different shapes of nanoparticles, gold nanoparticles (Au-NPs) with non-spherical shape, such as gold nanorods (Au-NR), are gaining particular attention for various applications because of their facile synthesis and modification. They can be conjugated with different molecules for biomedical applications, such as tumor imaging and therapy. Previously, we have shown that small sized Au-NPs possess distinct effects depending on the treatment modality; they protect against x-ray induced apoptosis while enhancing apoptosis induced by ultrasound and helium based cold atmospheric plasma. Therefore, this study is intended to investigate the effects of Au-NR, on x-ray (2.5 Gy) induced apoptosis as well as mediating molecular pathways in MOLT 4 cells in-vitro . The effect of Au-NR on x-ray induced apoptosis was determined by observing the changes in intracellular reactive oxygen species (ROS) formation and apoptotic signalling pathways. The results indicate that cells pre-treated with 10 nm size of Au-NR at a dose of 0.1 and 0.5 μg significantly enhanced apoptosis. Typical morphological changes were observed by using Giemsa staining which shows the enhanced apoptotic cell death in combination treatment. Loss of mitochondrial membrane potential, glutathione and intracellular calcium ion level was significantly enhanced; observed by using flow cytometry. Furthermore, western blot analysis was employed to determine the expression of caspase-3, and Bcl-2 family proteins. In this study we have shown for the first time that in combination treatment, Au-NR significantly enhanced the low dose of x-ray-induced apoptotic cell death. Our finding indicates that the combination treatment of cancer will be emerged as a critical approach to achieve remarkable anticancer effects.
利益披露 Disclosure
P. Jawaid, None..
M. Rehman, None..
A. H. Rajabali, None..
A. Enam, None.