| 贺美娟,王毅晖,余宏微,范旭辉,王 悍.PVCL-MnO2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[J].,2022,(10):1801-1805 |
| PVCL-MnO2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-MnO2 Nanoprobe for Radiosensitization and MRI Imaging of Glioblastoma Multiforme |
| 投稿时间：2022-01-04 修订日期：2022-01-26 |
| DOI：10.13241/j.cnki.pmb.2022.10.001 |
| 中文关键词: 放疗增敏 MRI成像 多形性胶质母细胞瘤 |
| 英文关键词: Radiosensitization MRI imaging Glioblastoma multiforme |
| 基金项目: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) |
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| 中文摘要: |
| 摘要 目的：探讨PVCL-MnO2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-MnO2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-MnO2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-MnO2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-MnO2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-MnO2颗粒粒径分布均匀，结构规整, 表现出良好的单分散性。PVCL-MnO2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-MnO2具有较好的T1-加权MRI成像效果，在尾静脉注射PVCL-MnO2 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-MnO2可实现多形性胶质母细胞瘤的放疗增敏及MRI成像。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the radiosensitization and MR Imging of PVCL-MnO2 nanoprobes on orthotopic glioblastoma multiforme. Methods: PVCL-MnO2 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-MnO2 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-MnO2 nanoprobes and radiotherapy, immunofluorescence, western blot and other techniques were utilized to evaluate the production of γ-H2AX, reactive oxygen species (ROS) and apoptosis-related proteins (Bax, Bcl-2). Finally, glioblastoma-bearing mice were injected with PVCL-MnO2 nanoprobes via tail vein and scanned by MRI at different time points. Results: PVCL-MnO2 nanoprobes possessed a uniform size distribution, well-defined structure and excellent monodispersity. The combination of PVCL-MnO2 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-MnO2 performed excellent in T1-weighted MRI imaging. The increasing signal at the tumor site was the most distinct at 4h post-injection of PVCL-MnO2. Then the signal began to decrease. Conclusion: The PVCL-MnO2 nanoprobe has potential for radiosensitization and MRI imaging of glioblastoma multiforme. |
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