PVCL-MnO_(2)纳米探针用于多形性胶质母细胞瘤的放疗增敏及MRI成像的实验研究  

Experimental Study of PVCL-MnO_(2) Nanoprobe for Radiosensitization and MRI Imaging of Glioblastoma Multiforme

作　　者：贺美娟 王毅晖[1] 余宏微 范旭辉 王悍[1] HE Mei-juan;WANG Yi-hui;YU Hong-wei;FAN Xu-hui;WANG Han(Department of Radiology,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,200080,China)

机构地区：[1]上海交通大学附属第一人民医院放射科,上海200080

出　　处：《现代生物医学进展》2022年第10期1801-1805,1840,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81871400);上海市教委重大项目(202101070002E00085);上海市科委重点项目(18441905000)。

摘　　要：目的:探讨PVCL-MnO_(2)对多形性胶质母细胞瘤的放疗增敏作用,并进行体内MRI成像研究。方法:制备PVCL-MnO_(2)纳米探针,利用透射电子显微镜(Transmission Electron Microscope,TEM)对其形态进行表征,并使用Image J分析其尺寸分布。采用细胞增殖-毒性实验(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT),测定PVCL-MnO_(2)协同放疗处理肿瘤细胞48 h后的细胞活性。将多形性胶质母瘤细胞瘤细胞进行PVCL-MnO_(2)共孵育后,协同放疗处理,分别使用免疫荧光,蛋白质印迹法等实验技术检测H2AX组蛋白异型的磷酸化形式(phosphorylated form of the histone protein H2AX,γ-H2AX),活性氧自由基(reactive oxygen species,ROS)的产生及Bax,Bcl-2凋亡相关蛋白的表达。PVCL-MnO_(2)尾静脉注射至原位多形性胶质母细胞瘤小鼠中,在不同的时间点进行MRI扫描,观察成像效果。结果:PVCL-MnO_(2)颗粒粒径分布均匀,结构规整,表现出良好的单分散性。PVCL-MnO_(2)联合放疗可有效增强DNA双链的断裂,ROS及促凋亡蛋白Bax的产生,同时下调了抗凋亡蛋白Bcl-2。MRI成像显示,PVCL-MnO_(2)具有较好的T_(1)-加权MRI成像效果,在尾静脉注射PVCL-MnO_(2)后4 h,肿瘤部位的信号增强最明显,随后信号开始下降。结论:PVCL-MnO_(2)可实现多形性胶质母细胞瘤的放疗增敏及MRI成像。Objective:To investigate the radiosensitization and MR Imging of PVCL-MnO_(2)nanoprobes on orthotopic glioblastoma multiforme.Methods:PVCL-MnO_(2)nanoprobes were prepared and characterized by transmission electron microscope(TEM).Meanwhile,the size distribution was analyzed by Image J.Then the cell viability of tumor cells treated by PVCL-MnO_(2)and radiotherapy for 48 h were determined by cell proliferation-toxicity test(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT).Moreover,C6 cells treated with PVCL-MnO_(2)nanoprobes and radiotherapy,immunofluorescence,western blot and other techniques were utilized to evaluate the production ofγ-H2AX,reactive oxygen species(ROS)and apoptosis-related proteins(Bax Bcl-2).Finally,glioblastoma-bearing mice were injected with PVCL-MnO_(2)nanoprobes via tail vein and scanned by MRI at different time points.Results:PVCL-MnO_(2)nanoprobes possessed a uniform size distribution,well-defined structure and excellent monodispersity.The combination of PVCL-MnO_(2)nanoprobes and radiotherapy could effectively enhance DNA double-strand breaks and the production of ROS and pro-apoptotic protein Bax.The expression of anti-apoptotic protein Bcl-2 was downregulated.MR imaging showed that PVCL-MnO_(2)performed excellent in T_(1)-weighted MRI imaging.The increasing signal at the tumor site was the most distinct at 4h post-injection of PVCL-MnO_(2).Then the signal began to decrease.Conclusions:The PVCL-MnO_(2)nanoprobe has potential for radiosensitization and MRI imaging of glioblastoma multiforme.

关 键 词：放疗增敏 MRI成像 多形性胶质母细胞瘤 

分 类 号：R-33[医药卫生] R445R730.5