临床神经外科杂志Issue(2)：93-98,6.DOI:10.3969/j.issn.1672-7770.2019.02.001
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
Hypoxia-responsive lipid-poly-radiosensitizer inhibits proliferation of glioma
摘要
Abstract
Objective To solve the bottleneck problem of improving radiosensitivity of glioma cells.Methods ALP-(MIs)n preparation and characterization : (1)If P-( MIs)25 was synthesized correctly, it was confirmed by 1 H-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 C 6／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. Results ALP-(MIs)25 preparation and characterization : (1)1 H-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 C 6cells (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 C 6／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 .关键词
缺氧响应/放疗增敏剂/脑胶质瘤Key words
hypoxic response / radiosensitizer/ glioma分类
医药卫生引用本文复制引用
XU Hao-yue,ZHAO Zong-ren,LI Shun..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,(2):93-98,6.基金项目
国家自然科学基金(81772665) （81772665）
