中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (3): 413-416.doi: 10.3969/j.issn.1673-8225.2012.03.007

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

血管生成靶向纳米粒子c(RGDyK)@SiO2@Fe3O4的合成及生物性能*

孙鹏飞1，曹向荣1，朱  浩1，焦宗宪2，张锋伟3，颉克蓉1   

  1. 1兰州大学第二医院，甘肃省兰州市  730030；兰州大学，2基础医学院， 3化学化工学院，甘肃省兰州市 730000
  • 收稿日期:2011-10-31 修回日期:2011-11-08 出版日期:2012-01-15 发布日期:2012-01-15
  • 作者简介:孙鹏飞，男，1973年生，副主任医师，副教授，硕士生导师。主要从事影像诊断及肿瘤放射治疗的相关研究。 sunpengfeiyy@msn.com
  • 基金资助:

    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。

Preparation and biological characterization of c(RGDyK)@SiO2@Fe3O4 nanoparticles targeted for angiogenesis  

Sun Peng-fei1, Cao Xiang-rong1, Zhu Hao1, Jiao Zong-xian2, Zhang Feng-wei3, Xie Ke-rong1   

  1. 1Lanzhou University Second Hospital, Lanzhou  730030, Gansu Province, China; 2College of Basic Medical Science, Lanzhou University, Lanzhou  730000, Gansu Province, China; 3College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, Gansu Province, China
  • Received:2011-10-31 Revised:2011-11-08 Online:2012-01-15 Published:2012-01-15
  • About author:Sun Peng-fei, Associate chief physician, Associate professor, Master’s supervisor, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China sunpengfeiyy@ msn.com
  • Supported by:

    the Fundamental Research Funds for the Central Universities, No.lzujbky-2009-154*

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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1.0 mg c(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24，48，72 h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40 nm，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24 h，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72 h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。
 

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

Abstract:

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 acid-loaded 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.

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