Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures
Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures
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DOI：
10.1021/acsnano.8b02038
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发表时间：
2018-05-01
期刊：
影响因子：
17.1
通讯作者：
Xing, Lei
中科院分区：
文献类型：
--
作者：
Cheng, Kai;Sano, Michael;Xing, Lei
基于纳米粒子的放射增敏剂即使在相对较低的浓度下也可以放大肿瘤组织的放射治疗效果，同时减少对周围健康组织的潜在副作用。在这项研究中，我们研究了由金(Au)和二氧化钛(Ti02)组成的杂化各向异性纳米结构，作为放射增敏剂用于三阴性乳腺癌(TNBC)的放射治疗。与其他金基放射增敏剂相比，哑铃型Au-Ti02纳米粒子(DAT)在放射治疗中表现出协同治疗作用，这主要是因为高原子序数金属与介质氧化物之间在界面上存在着强烈的不对称电耦合。由X射线辐射引发的DAT产生二次电子和活性氧物种(ROS)可以显著增强辐射效应。DAT被癌细胞吞噬后，在X射线照射下可产生大量ROS，最终诱导癌细胞凋亡。在TNBC肿瘤模型中，在放射增敏放射治疗的DAT摄取下，成功地证明了显着的肿瘤生长抑制和总体存活率的提高。
Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio sensitized radiation therapy.