Yu Bo, Liu Ting, Du Yanxin, Luo Zuandi, Zheng Wenjie, Chen Tianfeng
Department of Chemistry, Jinan University, Guangzhou 510632, China.
Orthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.
Colloids Surf B Biointerfaces. 2016 Mar 1;139:180-9. doi: 10.1016/j.colsurfb.2015.11.063. Epub 2015 Dec 9.
Resistance of cancer to radiotherapy and/or chemotherapy is one of the important reasons of clinical treatment failure and recurrence. Chemoradiation is an optional method to over-coming of radioresistance and chemoresistance. Selenium nanoparticles (SeNPs) with special chemical and physical properties, has been identified as a novel nanocarrier and therapy agent with broad-spectrum anticancer activities due to generate ROS in cells. Herein, X-ray responsive selenium nanoparticles were facilely fabricated by using PEG as surface decorator and template. This nanosystem (PEG-SeNPs) demonstrated X-ray responsive property that was attributed to its amorphous characteristic. Interestingly, the nanosystem demonstrated significant radiosensitization effects with X-ray. Specifically, co-treatment of cancer cells with PEG-SeNPs and X-ray significantly and synergistically enhanced the cells growth inhibition through induction of cell apoptosis, as evidenced by DNA fragmentation and activation of caspase-3. In the cell model, we found that internalized nanoparticles could degrade upon X-ray exposure, which further confirm the X-ray responsive property of the nanoparticles. Moreover, the nanosystem could significantly induced intracellular ROS generation in a time-dependent manner, which peaked at about 40min and gradually decreased thereafter. As a results, ROS overproduction led to mitochondria fragmentation and the cell apoptosis. Taken together, this study provides a novel strategy for rational design and facile synthesis of chemo-radio therapeutic radiosensitization nanomaterials.
癌症对放疗和/或化疗的耐药性是临床治疗失败和复发的重要原因之一。放化疗是克服放疗耐药性和化疗耐药性的一种可选方法。具有特殊化学和物理性质的硒纳米颗粒(SeNPs),由于能在细胞中产生活性氧(ROS),已被确定为一种具有广谱抗癌活性的新型纳米载体和治疗剂。在此,通过使用聚乙二醇(PEG)作为表面修饰剂和模板,简便地制备了X射线响应性硒纳米颗粒。这种纳米系统(PEG-SeNPs)表现出X射线响应特性,这归因于其无定形特征。有趣的是,该纳米系统在X射线下表现出显著的放射增敏作用。具体而言,PEG-SeNPs与X射线联合处理癌细胞,通过诱导细胞凋亡显著且协同地增强了对细胞生长的抑制作用,DNA片段化和半胱天冬酶-3的激活证明了这一点。在细胞模型中,我们发现内化的纳米颗粒在X射线照射下会降解,这进一步证实了纳米颗粒的X射线响应特性。此外,该纳米系统能以时间依赖性方式显著诱导细胞内ROS生成,在约40分钟时达到峰值,此后逐渐下降。结果,ROS的过量产生导致线粒体碎片化和细胞凋亡。综上所述,本研究为合理设计和简便合成放化疗治疗放射增敏纳米材料提供了一种新策略。