核定位序列修饰的二氧化钛纳米颗粒对胶质瘤U251细胞的放射增敏作用

Titanium dioxide nanoparticles coupled with nuclear localization sequence increases the radiosensitivity of U251 glioma cells

目的研究核定位序列（nuclear localization sequence，NLS）修饰的二氧化钛（titanium dioxide，TiO2）纳米颗粒对胶质瘤U251细胞放射敏感性的作用。方法合成并表征具有细胞核靶向性的TiO2-NLS纳米颗粒，分别用纳米颗粒和电离辐射单独或联合处理U251细胞，流式细胞仪检测活性氧（ROS）含量和细胞凋亡率，γ-H2AX焦点（foci）染色检测DNA损伤修复的情况，细胞克隆形成实验检测细胞放射敏感性的改变。结果NLS修饰可促进TiO2纳米颗粒进入U251细胞核，与未修饰的TiO：纳米颗粒相比，TiO2-NLS纳米颗粒可促进电离辐射诱导的细胞凋亡（t：8．96，P〈0．05），细胞克隆实验显示，TiO2-BSA纳米颗粒组的放射增敏比为1．18，TiO2-NLS纳米颗粒处理组的放射增敏比为1．29，两组比较，差异有统计学意义（t=14．72，P〈0．05）。结论具有细胞核靶向性的TiO2纳米颗粒能够增强胶质瘤U251细胞的放射敏感性。

Objective To investigate the effects of titanium dioxide （ TiO2 ） nanoparticles coupled with nuclear localization sequence （NLS） on the radiosensitivity of U251 glioma ceils. Methods Synthesis and characterization of the TiO2-NLS nanoparticles with nuclear targeting property. U251 cells were treated with nanoparticles and/or ionizing radiation. Flow cytometry analysis was performed to measure the ROS content and the cell apoptotic percentage. The DNA damage was detected by using γ-H2AX foci staining. Clonogenic survival assay was used to evaluate the radiosensitivity of U251 cells. Results NLS modification promoted nuclear translocation of TiO2 nanoparticles. Compared with the control nanoparticles, TiO2-NLS treatment increased radiation-induced cell apoptosis （ t = 8.96, P 〈 0.05 ）. Clonogenic survival assay showed the radiosensitization ratios of TiOz nanoparticle-treated group and TiO2-NLSnanoparticle-treated group were 1. 18 and was 1.29, respectively. These two ratios had statistically difference （t = 14.72, P 〈 O. 05）. Conclusions Nuclear targeting TiO2 nanoparticles enhances the radiosensitivity of U251 glioma cells.