Tao Weiyong, Tuo Zhan, Wu Feige, Mu Ketao, Xu Cunjing, Shi Yuxiao, Sun Zeyu, Wang Yifan, Li Yan, Zhong Zhenyu, Zhou Lei, Wang Jianglin, Liu Jie, Du Yingying, Zhang Shengmin
Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Regen Biomater. 2022 Jul 5;9:rbac045. doi: 10.1093/rb/rbac045. eCollection 2022.
The tumor microenvironment with overexpressed hydrogen peroxide (HO) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with HO to produce •OH and release Cu. Then, the Cu further depletes GSH to generate Cu for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.
过氧化氢（HO）过表达且抗氧化系统（谷胱甘肽，GSH）增强的肿瘤微环境，对于纳米治疗的可及性而言成为了一把双刃剑。由于活性氧（ROS）很容易被已形成的抗氧化网络淬灭，因此诸如化学动力学疗法（CDT）和放射疗法（RT）等基于ROS杀死癌细胞的治疗方法会严重减弱。为了克服这些限制，人们开发了一种生物活性纳米球系统，通过使用基于牛血清白蛋白（BSA）的生物活性纳米球来调节细胞内氧化应激，以增强放射化学动力学联合治疗，该纳米球是由BSA与生成的硫化铜铋纳米点和二烯丙基三硫化物（DATS）组装而成。硫化铜铋纳米点与HO反应生成•OH并释放Cu。然后，Cu进一步消耗GSH以通过类芬顿反应方式生成更多的•OH。这样的级联反应可以引发•OH生成和GSH消耗以实现CDT。由BBCD纳米球中的DATS触发的ROS升高进一步加剧了4T1细胞中氧化应激增加导致的氧化还原平衡的破坏。随着氧化应激增加和高Z元素Bi的敏化作用，实现了增强的放射化学动力学联合治疗。当前的工作通过使用共组装的生物活性纳米球作为氧化应激的放大器，为大多数实体瘤提供了一种增强的放射化学动力学联合治疗方法。
