Department of Chemistry, Jinan University , Guangzhou 510632, P.R. China.
Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, P.R. China.
ACS Nano. 2017 May 23;11(5):4848-4858. doi: 10.1021/acsnano.7b01346. Epub 2017 May 9.
Radiotherapy is an important regime for treating malignant tumors. There is interest in the development of radiosensitizers to increase the local treatment efficacy under a relatively low and safe radiation dose. In this study, we designed Au@Se-R/A nanocomposites (Au@Se-R/A NCs) as nano-radiosensitizer to realize synergistic radiochemotherapy based on the radiotherapy sensitization property of Au nanorods (NRs) and antitumor activity of Se NPs. In vitro studies show that the combined treatment of A375 melanoma cells in culture with NCs and X-ray induces cell apoptosis through alteration in expression of p53 and DNA-damaging genes and triggers intracellular ROS overproduction, leading to greatly enhanced anticancer efficacy. Further studies using clinically used radiotherapy equipment demonstrate that the combined treatment of NCs and X-ray significantly inhibits the tumor growth in vivo and shows negligible acute toxicity to the major organs. Taken together, this study provides a strategy for clinical translation application of nanomedicne in cancer radiochemotherapy.
放射疗法是治疗恶性肿瘤的重要手段。人们对开发放射增敏剂很感兴趣，希望在相对较低和安全的辐射剂量下，提高局部治疗效果。在这项研究中，我们设计了 Au@Se-R/A 纳米复合材料（Au@Se-R/A NCs）作为纳米增敏剂，利用金纳米棒（NRs）的放射增敏特性和 Se NPs 的抗肿瘤活性，实现协同放化疗。体外研究表明，将 NCs 与 X 射线联合用于培养的 A375 黑色素瘤细胞，通过改变 p53 和 DNA 损伤基因的表达，诱导细胞凋亡，并引发细胞内 ROS 过度产生，从而大大增强了抗癌效果。进一步使用临床使用的放射治疗设备进行的研究表明，NCs 与 X 射线的联合治疗可显著抑制体内肿瘤生长，对主要器官几乎没有明显的急性毒性。综上所述，本研究为癌症放化疗中纳米医学的临床转化应用提供了一种策略。
