血管生成靶向纳米粒子c(RGDyK)@SiO_2@Fe_3O_4的合成及生物性能  

Preparation and biological characterization of c(RGDyK)@SiO_2@Fe_3O_4 nanoparticles targeted for angiogenesis

作　　者：孙鹏飞[1] 曹向荣[1] 朱浩[1] 焦宗宪[2] 张锋伟 颉克蓉[1] 

机构地区：[1]兰州大学第二医院,甘肃省兰州市730030 [2]兰州大学,基础医学院,甘肃省兰州市730000 [3]化学化工学院,甘肃省兰州市730000

出　　处：《中国组织工程研究与临床康复》2012年第3期413-416,共4页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：兰州大学中央高校基本科研业务费专项资金资助(lzujbky-2009-154),课题名称:血管生成靶向纳米粒子(c(RGDyK)@SiO2@Fe3O4)的合成及生物性能~~

摘　　要：背景:SiO2含有较多的羟基官能团,可进一步功能化而与靶向性配体相偶联,从而拓展Fe3O4@SiO2纳米粒子在生物医药领域的应用。目的:探讨靶向性纳米粒子c(RGDyK)@SiO2@Fe3O4)的合成方法,并对其性能进行测试。方法:采用一壶化学共沉淀法合成油酸修饰的疏水性Fe3O4纳米粒子,采用反相微乳液法合成生物相容性Fe3O4@SiO2复合纳米粒子;以3-氨丙基三乙氧基硅烷为偶联剂将复合粒子中SiO2表面的羟基氨基化、醛基化,加入1.0mgc(RGDyK)多肽,超声震荡下反应生成c(RGDyK)@SiO2@Fe3O4纳米粒子。将Fe3O4@SiO2或c(RGDyK)@SiO2@Fe3O4与人脐静脉细胞融合细胞(EA.hy926)共培养24,48,72h进行检测。结果与结论:实验合成的Fe3O4@SiO2复合纳米粒子的平均粒径为40nm,应用3-氨丙基三乙氧基硅烷可将c(RGDyK)成功耦合于复合粒子的SiO2表面。Fe3O4@SiO2或c(RGDyK)@SiO2@Fe3O4与EA.hy926共培养24h,EA.hy926细胞活性明显增高(P<0.05),以c(RGDyK)@SiO2@Fe3O4的作用更明显;共培养72h后,细胞活性在各组间差异无显著性意义(P>0.05)。电镜观察发现,EA.hy926细胞对靶向性c(RGDyK)@SiO2@Fe3O4粒子的吞噬能力明显强于非靶向性Fe3O4@SiO2粒子。说明实验合成的c(RGDyK)@SiO2@Fe3O4纳米粒子具有良好的生物相容性、超顺磁性及较高的血管内皮细胞靶向性,是一种优良的生物材料。BACKGROUND：SiO2 has a great amount of hydroxyl groups,It can be further functionalized to couple targeting ligand in order to expand the application of Fe3O4@SiO2 nanoparticles in the biomedical field.OBJECTIVE：To investigate the preparation method of targeted c（RGDyK）@SiO2@Fe3O4 nanoparticles（NPs） and its property testing.METHODS：Oleic acidloaded hydrophobic Fe3O4 NPs were prepared via a pot chemical coprecipitation,and the biocompatible Fe3O4@SiO2 compound NPs were synthesized with a reverse microemulsion.By means of the 3-aminopropyl triethoxysilan（APTMS） as couplant,the hydroxyl groups of SiO2 surface in compound particles were changed into amino or aldehyde groups.Then 1.0 mg of c（RGDyK） peptide was added into the reaction system under ultrasound shake in order to prepare c（RGDyK）@SiO2@ Fe3O4 NPs.The Fe3O4@SiO2 or c（RGDyK）@SiO2@Fe3O4 NPs were co-cultured with EA.hy926 cells for detection at 24,48 and 72 h hours.RESULTS AND CONCLUSION：Fe3O4@SiO2 NPs prepared by a pot chemical coprecipitation and reverse microemulsion had a mean diameter of 40 nm,and c（RGDyK） peptide was successfully connected to SiO2 surface of compound NPs via APTMS.After EA.hy926 cells were cultured accompanied with Fe3O4@SiO2 or c（RGDyK）@SiO2@Fe3O4 NPs for 24 hours,the cell activity was significantly improved（P 0.05）,especially with the c（RGDyK）@SiO2@Fe3O4 NPs,and there was no difference in cell activity between the control group and c（RGDyK）@SiO2@Fe3O4 group at 72 hours（P 0.05）.Electron microscopy showed that the ability of EA.hy926 cells phagocytizing targeted c（RGDyK）@SiO2@Fe3O4 NPs was more stronger than no-targeted Fe3O4@SiO2 NPs at 24 hours of cell culture.The c（RGDyK）@SiO2@Fe3O4 NPs are a kind of excellent biomaterial because of their biocompatibility,superparamagnetism and higher ability of targeted for vascular endothelial cells.

关 键 词：微乳液法 二氧化硅 四氧化三铁 四甲基偶氮唑盐 RGD肽 生物相容性 超顺磁性 靶向性 

分 类 号：R318[医药卫生—生物医学工程]