Li Na, Yu Longhai, Wang Jianbo, Gao Xiaonan, Chen Yuanyuan, Pan Wei, Tang Bo
College of Chemistry , Chemical Engineering and Materials Science , Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong , Key Laboratory of Molecular and Nano Probes , Ministry of Education , Institute of Molecular and Nano Science , Shandong Normal University , Jinan 250014 , P. R. China . Email:
Radiation Department , Qilu Hospital of Shandong University , Jinan 250100 , P. R. China.
Chem Sci. 2018 Feb 28;9(12):3159-3164. doi: 10.1039/c7sc04458e. eCollection 2018 Mar 28.
Radiation therapy (RT) has been widely used for malignant tumor treatment. However, the large dosage of ionizing radiation and high frequency of radiotherapy in clinical cancer therapy cause severe damage to normal tissues adjacent to tumors. Therefore, how to increase the local treatment efficacy and reduce the damage to normal tissues has been a challenge for RT. Herein, we developed a novel strategy for enhanced RT based on a mitochondria targeted titanium dioxide-gold nanoradiosensitizer. When irradiated with X-rays, the nanosensitizer could produce reactive oxygen species (ROS) in the mitochondria, which induced the domino effect on the ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. A colony formation assay indicated that the cell survival rate when incubated with the mitochondrial targeted nanosensitizer was significantly lower than that of non-targeted groups. As demonstrated by experiments, the tumor was significantly suppressed even just once RT with the nanosensitizer.
放射治疗（RT）已广泛应用于恶性肿瘤治疗。然而，临床癌症治疗中高剂量的电离辐射和高频率的放射治疗会对肿瘤邻近的正常组织造成严重损伤。因此，如何提高局部治疗效果并减少对正常组织的损伤一直是放射治疗面临的挑战。在此，我们基于线粒体靶向二氧化钛-金纳米放射增敏剂开发了一种增强放射治疗的新策略。当用X射线照射时，纳米增敏剂可在线粒体中产生活性氧（ROS），从而引发ROS爆发的多米诺效应。过量产生的ROS在线粒体中积累，导致线粒体崩溃和不可逆的细胞凋亡。集落形成试验表明，与线粒体靶向纳米增敏剂孵育时的细胞存活率显著低于非靶向组。实验证明，即使仅用纳米增敏剂进行一次放射治疗，肿瘤也会受到显著抑制。
