VEGFR-2靶向超顺磁性氧化铁磁性纳米探针构建及肝癌细胞磁共振分子成像

发布时间：2018-01-26 21:16

本文关键词： VEGFR- 超顺磁性氧化铁壳聚糖肿瘤靶向磁共振分子成像　出处：《中国老年学杂志》2017年14期 　论文类型：期刊论文

【摘要】：目的制备血管内皮生长因子受体(VEGFR)-2靶向磁共振(MR)分子探针,探讨其对肝癌细胞的特异性靶向作用。方法采用共沉淀法制备超顺磁性氧化铁(SPIO),用壳聚糖对其表面进行修饰,耦联anti-VEGFR2抗体,制备VEGFR-2靶向MR分子探针(anti-VEGFR2-CS@SPION),以未修饰的SPIO纳米粒作为对照组。DLS法测量粒径大小、分布及Zeta电位,3.0T MR检测T2弛豫率。MTT法评价探针的安全性,通过激光共聚焦显微镜检测以及普鲁士蓝染色的方法验证探针与肝癌细胞结合的特异性。3.0T MR观察探针的体外MR成像能力。结果 SPIO和antiVEGFR2-CS@SPION的粒径分别为20.6 nm和38.4 nm;Zeta电位分别为-(20.3±1.32)m V、(3.58±1.28)m V。T2弛豫率分别为0.179×10~6M~(-1)S~(-1)、0.201×106M~(-1)S~(-1)。细胞毒性实验表明探针在高浓度下对细胞没有毒性;激光共聚焦显微镜检测显示,抗体探针与Hep G2细胞特异性结合;antiVEGFR2-CS@SPION与Hep G2细胞孵育后经普鲁士蓝染色,细胞内见较多的蓝染颗粒,而单纯SPIO组细胞内未见蓝色颗粒。体外MR成像显示,anti-VEGFR2-CS@SPION组、单纯SPIO组和空白对照组的T2值分别为(55.6±1.4)ms、(99.8±0.77)ms和(110.8±0.95)ms,差异有统计学意义(F=317.547,P0.01)。结论壳聚糖修饰和SPIO标记的anti-VEGFR2抗体探针具有良好的生物学特性和体外肝癌细胞MR显像能力。
[Abstract]:Objective to prepare vascular endothelial growth factor receptor (VEGFR-2) targeted Mr Mr probe (MRM). Methods the superparamagnetic ferric oxide (SPIOO) was prepared by coprecipitation method. The surface of the superparamagnetic ferric oxide was modified by chitosan and coupled with anti-VEGFR2 antibody. VEGFR-2 targeted Mr molecular probe anti-VEGFR2-CSBSPIONN was prepared and the particle size was measured using unmodified SPIO nanoparticles as control group. The safety of the probe was evaluated by Zeta potential 3.0T Mr detection of T2 relaxation rate. Laser confocal microscopy and Prussian blue staining were used to verify the ability of in vitro Mr imaging of the probe. The particle sizes of SPIO and antiVEGFR2-CS@SPION were 20.6 nm and 38.4 nm, respectively. The Zeta potential was 20.3 卤1.32mV, respectively. The relaxation rates of 3.58 卤1.28 m V. T2 were 0.179 脳 10 ~ (6) M ~ (-1) M ~ (-1) and 0.179 脳 10 ~ (6) M ~ (-1) 路m ~ (-1), respectively. The cytotoxicity test showed that the probe was not toxic to cells at high concentration. Laser confocal microscopy showed that the antibody probe was specifically bound to Hep G2 cells. After antiVEGFR2-CS@SPION was incubated with Hep G2 cells, more blue staining granules were found in the cells after Prussian blue staining. In vitro Mr imaging showed anti-VEGFR2-CSSPION group. The T2 values of simple SPIO group and blank control group were 99.8 卤0.77 Ms and 110.8 卤0.95 Ms, respectively. The difference was statistically significant (317.547). Conclusion Chitosan-modified and SPIO labeled anti-VEGFR2 antibody probe has good biological characteristics and in vitro hepatocellular carcinoma cell Mr imaging ability.
【作者单位】：延边大学附属医院影像一科;延边大学药学院;延边大学解剖学教研室;
【基金】：国家自然科学基金资助项目(No.81160176) 吉林省科技发展计划项目(20150101199JC)
【分类号】：R445.2;R735.7
【正文快照】： 磁共振(MR)分子成像可以实现肝癌特异性诊断和早期检测。血管内皮生长因子(VEGF)及其受体(VEGFR)是重要的血管生成显像剂,VEGF与VEGFR在肿瘤细胞的表达程度与肿瘤新生血管的增殖、侵袭、转移及预后相关[1]。VEGF可以与3种特异性VEGFR结合,其中VEGFR-2是血管内皮细胞表面与VEGF

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