[1]徐浩月,赵宗仁,李顺,等.缺氧响应特性的脂质-聚合物放疗增敏剂抑制脑胶质瘤增殖的研究[J].临床神经外科杂志,2019,16(2):93-98.[doi:10.3969/j.issn.1672-7770.2019.02.001]
 XU Hao-yue,ZHAO Zong-ren,LI Shun,et al.Hypoxia-responsive lipid-poly-radiosensitizer inhibits proliferation of glioma[J].Journal of Clinical Neurosurgery,2019,16(2):93-98.[doi:10.3969/j.issn.1672-7770.2019.02.001]
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缺氧响应特性的脂质-聚合物放疗增敏剂抑制脑胶质瘤增殖的研究()
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《临床神经外科杂志》[ISSN:1672-7770/CN:32-1727/R]

卷:
16
期数:
2019年第2期
页码:
93-98
栏目:
转化医学专题
出版日期:
2019-04-17

文章信息/Info

Title:
Hypoxia-responsive lipid-poly-radiosensitizer inhibits proliferation of glioma
作者:
徐浩月赵宗仁李顺赵亮叶成坤于如同刘洪梅
221002 徐州,徐州医科大学神经系统疾病研究所
Author(s):
XU Hao-yue ZHAO Zong-ren LI Shun et al.
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, China
关键词:
缺氧响应放疗增敏剂脑胶质瘤
Keywords:
hypoxic responseradiosensitizerglioma
分类号:
R739.41
DOI:
10.3969/j.issn.1672-7770.2019.02.001
文献标志码:
A
摘要:
【摘要】目的 研究提高脑胶质瘤细胞的放疗(radiotherapy,RT)敏感性的药物及其效果。方法制备有缺氧响应特性的脂质-聚合物[ALP-(MIs)n]放疗增敏剂,并检测其性质:(1)用核磁共振(1H-NMR)检测聚甲硝唑[ALP-(MIs)25]是否合成成功;(2)Nano-ZS粒度/Zeta电位测定仪检测实验组ALP-(MIS)25和对照组聚乳酸羟基乙酸共聚物(PLGA)聚合物(AL-PLGA)在常氧和缺氧环境下的粒径变化,透射电镜观察脂质-聚合物的形态。细胞水平检测:用克隆集落形成实验检测ALP-(MIS)25对C6细胞株放疗的增敏性。动物水平检测:(1)构建稳转荧光素酶的C6细胞原位小鼠脑胶质瘤模型;(2)检测肿瘤内缺氧环境;(3)检测小鼠脑胶质瘤的荧光素酶强度,统计小鼠的生存时间。结果ALP-(MIS)n的制备及其性质:(1)ALP-(MIS)n合成成功;(2)ALP-(MIS)n和 AL-PLGA构建成功,电镜观察示为圆形结构,ALP-(MIS)n直径为(88.81±0.98)nm,AL-PLGA直径为(80.38±1.07)nm;相比较于常氧环境下,缺氧环境下ALP-(MIS)25的水粒学直径增大,圆形结构破坏;而AL-PLGA在缺氧环境下水粒学直径和形态结构均未发生改变。克隆集落形成实验结果显示,与PBS+RT组、AL-PLGA+RT组相比,ALP-(MIS)n+RT组的C6细胞株克隆形成率明显下降,差异有统计学意义(P<0.01)。稳转荧光素酶的C6细胞原位小鼠脑胶质瘤模型构建成功;缺氧探针免疫荧光实验结果显示脑胶质瘤组织缺氧。与PBS组、PBS+RT组、AL-PLGA+RT组相比,ALP-(MIs)25+RT组小鼠的胶质瘤增殖速度最慢,中位生存期最长,差异有统计学意义(P<0.001,P<0.05)。结论ALP-(MIS)n联合放射治疗在缺氧环境下可有效抑制脑胶质瘤增殖。
Abstract:
Abstract: ObjectiveTo solve the bottleneck problem of improving radiosensitivity of glioma cells. MethodsALP-(MIs)n preparation and characterization: (1)If P-(MIs)25 was synthesized correctly, it was confirmed by 1H-NMR assay. (2)Under normoxic and hypoxic conditions, the Malvern ZetasizerNanoZS was used to measure the mean diameter of ALP-(MIs)25 and AL-PLGA. The morphology of ALP-(MIs)25 and AL-PLGA were observed by TEM. In Vitro analysis: The radiosensitity of ALP-(MIs)25on C6 cells were detected by clone formation assay. In Vivo analysis: (1)Gliomabearing mice were prepared by intracranialinjection C6/Luci/GFP cells. (2) Detection of hypoxic environment in tumors. (3) Tumor growth of C6 bearing mice were monitored by in vivo realtime fluorescence imaging system to monitor the anti-tumor effect of ALP-(MIs)25. The survival time was calculated from the day of glioma cellinoculation (0 day) to the death day. ResultsALP-(MIs)25 preparation and characterization: (1)1H-NMR spectra assay suggested that P-(MIs)25 was synthesized correctly. (2) The average diameters of ALP-(MIs)25 and AL-PLGA were approximately (88.81±0.98)nm and (80.38±1.07)nm. The TEM images suggested that the AL-PLGA and ALP-(MIs)25 were spherical NPs with a unimodal size distribution under normoxic conditions. In sharp contrast, the conformation of ALP-(MIs)25 was disassembled, and the conformation of AL-PLGA remained unchanged under hypoxic conditions. In Vitro analysis: The results of colony formation assay showed that, compared with PBS+RT group and AL-PLGA+RT group, the plating efficiency ofALP-(Mis)25+RT was significantly decreased in C6cells (P<0.01), and the sensitization enhancement ratio (SERD0) of C6 cells was 1.34. In Vivo analysis: (1) The orthotopic transplantation tumor model was successfully established with C6/Luci/GFP cells. (2) The results of hypoxia probe immunofluorescence showed that hypoxia was present in glioma tissues. (3) Compared with other experimental groups, ALP-(MIs)25+RT group suppressed tumor progression, prolonged survival time of the mice more effectively (P<0.001,P<0.05). Conclusion ALP-(MIs)25 combined with radiotherapy can effectively inhibit the proliferation of glioma.
更新日期/Last Update: 2019-04-17