多功能铁铋复合纳米粒对胶质母细胞瘤的放疗增敏作用  

Fabrication of multifunctional bismuth-doped iron nanoparticle and its radiotherapy sensitization in glioblastoma

作　　者：牛媛媛[1] 于明[1] 杜凤移[2] 陈思远[1] 赵天[3] 徐宇浩[1] 周倩文[1] 许修健 Niu Yuan-yuan Yu Ming Du Feng-yi Chen Si-yuan Zhao Tian Xu Yu-hao Zhou Qian-wen Xu Xiu-jian(Department of Neurology 3Department of Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China 2Jiangsu University Medical School, Zhenjiang 212013, Jiangsu Province, China)

机构地区：[1]江苏大学附属医院神经内科,江苏省镇江市212001 [2]江苏大学医学院,江苏省镇江市212013 [3]江苏大学附属医院医学影像科,江苏省镇江市212001

出　　处：《中国组织工程研究》2017年第18期2821-2827,共7页Chinese Journal of Tissue Engineering Research

基　　金：江苏省"333工程"科研项目(BRA2014173);江苏省"六大人才高峰"科研项目(WSN-038)~~

摘　　要：背景:透明质酸功能化的铁铋复合纳米颗粒是一种有效MRI对比剂,同时又可作为放疗增敏剂。目的:制备透明质酸功能化的铁铋复合纳米颗粒,观察其对胶质母细胞瘤U87MG的放疗增敏作用。方法:通过水热聚醇法制备透明质酸功能化的铁铋复合纳米颗粒HA-Bi IOPs。(1)细胞毒性实验:取对数生长期的人胶质母细胞瘤细胞株U87MG与大鼠血管平滑肌细胞,均以含0,12.5,25,50,100,200,400 mg/L HA-Bi IOPs的培养液培养48 h,计算细胞增殖率;(2)组织相容性实验:在ICR小鼠尾静脉注射HA-Bi IOPs溶液,观察小鼠脏器病理变化;(3)细胞吞噬实验:将HA-Bi IOPs与U87MG细胞共培养6 h,普鲁士蓝观察纳米颗粒是否被细胞吞噬;(4)放疗增敏实验:取对数生长期的U87MG细胞,分组培养:对照组以培养液培养;放疗组分别给予0,3,6,9 Gy的X射线照射;HA-Bi IOPs组分别加入含0,12.5,25,50,100,200,400 mg/L HA-Bi IOPs的培养液;联合组,先加入含0,12.5,25,50,100,200,400 mg/L HA-Bi IOPs的培养液,再给予0,3,6,9 Gy的X射线照射。24 h后,检测细胞增殖率及克隆形成率。结果与结论:(1)不同质量浓度的HA-BiI OPs对血管平滑肌细胞和U87MG细胞增殖无明显影响;(2)尾静脉注射HA-BiI OPs溶液后,小鼠脏器未发生病理变化;(3)共培养6 h后,HA-BiI OPs纳米颗粒可被U87MG细胞吞噬;(4)U87MG细胞增殖率与HA-BiI OPs质量浓度(0-200 mg/L)和放射剂量(0-9 Gy)有明显的线性负相关,尤其是在6 Gy X射线照射下200 mg/L HA-BiI OPs对细胞增殖率下降至(41±7)%。选用100 mg/L HA-BiI OPs、6 Gy X射线照射进行克隆形成实验,联合组U87MG细胞增殖率明显低于空白对照组、放疗组(P<0.05);(5)结果表明,透明质酸功能化的铁铋复合纳米颗粒对胶质母细胞瘤具有显著的放疗增敏作用。BACKGROUND： Bismth-doped iron nanoparticles modified by hyaluronic acid（HA-Bi IOPs） not only act as an effective MRI contrast agent, but also as a radiotherapy sensitizer. OBJECTIVE： To fabricate the HA-Bi IOPs and to observe its effect to enhance the radiosensitivity of glioblastoma cells U87 MG under X-ray radiation. METHODS： HA-Bi IOPs were synthesized using hydrothermal polyol method.（1） Cytotoxicity： A cytotoxicity test was carried out on U87 MG cells and rat vascular smooth muscle cells（VSMCs）. Cell proliferation rate of two kinds of cells cultured with different concentrations of HA-Bi IOPs（0, 12.5, 25, 50, 100, 200, 400 mg/L） at 24 hours after culture were determined by cell counting kit-8 assay.（2） Histological analysis： ICR mice were sacrificed after intravenous injection of HA-Bi IOPs, and pathological changes of mouse visceral organs were observed under an optical microscope.（3） Cellular uptake： The HA-Bi IOPs after entered into the cytoplasm were observed by Prussian blue staining.（4） Radiosensitization test： U87 MG cells at Logarithmic growth stage were cultured in culture medium as control group, subjected to X-ray irradiation（0, 3, 6, 9 Gy） as radiotherapy group, cultured in HA-Bi IOPs（0, 12.5, 25, 50, 100, 200 and 400 mg/L） as HA-Bi IOPs group or subjected to HA-Bi IOPs culture plus X-ray irradiation as combined therapy group. Then, the cell proliferation rate and cloning efficiency were measured at 24 hours after treatment. RESULTS AND CONCLUSION：（1） The HA-Bi IOPs at different concentrations were non-cytotoxic for VSMC and U87 MG cells.（2） After intravenous injection of HA-Bi IOPs, there was no obvious toxicity to the mouse susceptible organs.（3） After 6 hours of culture, the HA-Bi IOPs could be internalized by U87 MG cells.（4） The proliferation rate of U87 cells was negatively correlated with the concentration of HA-Bi IOPs（0-200 mg/L） and X-ray dose（0-9 Gy）. Especially, the combination of 6 Gy X-ray irradiation with 2

关 键 词：生物材料 纳米材料 铁铋复合纳米材料 水热聚醇法 放疗增敏 透明质酸 人胶质母细胞瘤细胞 生物相容性 杀伤肿瘤 细胞增殖率 

分 类 号：R318[医药卫生—生物医学工程]