| 吴琼雅,史景云,张颉,张霖倩,赵印敏,唐亮,陈芸,贺晓东,刘辉,粟波.制备肿瘤血管生成双靶点RGD10-NGR9-超顺磁性纳米氧化铁[J].中国医学影像技术,2013,29(9):1418~1422 |
| 制备肿瘤血管生成双靶点RGD10-NGR9-超顺磁性纳米氧化铁 |
| Preparation of ανβ3 integrin and aminopeptidase N dual-targeting RGD10-NGR9-superparamagnetic iron oxide |
| 投稿时间：2013-02-19 修订日期：2013-06-25 |
| DOI： |
| 中文关键词: 血管生成 磁共振成像 超顺磁性氧化铁 对比剂 |
| 英文关键词:Angiogenesis Magnetic resonance imaging Ultrasmall superparamagnetic iron oxide Contrast media |
| 基金项目:上海市科委资助项目(0952nm05900、09411960500、10411967600)。 |
| 作者 | 单位 | E-mail | | 吴琼雅 | 同济大学附属上海市肺科医院放疗科, 上海 200433 | | | 史景云 | 同济大学附属上海市肺科医院影像科, 上海 200433 | | | 张颉 | 同济大学附属上海市肺科医院中心实验室, 上海 200433 | | | 张霖倩 | 华东理工大学材料科学与工程学院, 上海 200237 | | | 赵印敏 | 同济大学附属上海市肺科医院中心实验室, 上海 200433 | | | 唐亮 | 同济大学附属上海市肺科医院中心实验室, 上海 200433 | | | 陈芸 | 同济大学附属上海市肺科医院放疗科, 上海 200433 | | | 贺晓东 | 同济大学附属上海市肺科医院放疗科, 上海 200433 | | | 刘辉 | 同济大学附属上海市肺科医院放疗科, 上海 200433 | | | 粟波 | 同济大学附属上海市肺科医院中心实验室, 上海 200433 | su_bo_s@hotmail.com |
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| 中文摘要: |
| 目的 构建新型肿瘤血管生成靶向双靶点RGD10-NGR9-超顺磁性氧化铁纳米颗粒,并检测其物理性质。方法 设计合成双靶点RGD10-NGR9杂合肽,以固相合成法异硫氰酸荧光素(FITC)标记杂合肽,检测其与人脐静脉内皮细胞的体外结合能力。采用共沉淀法制备核芯粒径8~12 nm的超顺磁性氧化铁,包覆葡聚糖。以环氧氯丙烷活化葡聚糖,共价耦联靶向多肽,制备靶向多肽—网状交联葡聚糖—超顺磁性氧化铁复合粒子。采用透射电子显微镜观测粒子大小、X射线衍射仪测试粒子晶型及组成,红外光谱仪分析粒子表面包覆物质表征,纳米粒度仪测定Zeta电位,振动样品磁强计仪测定磁化强度。结果 双靶点杂合肽FITC-RGD10-NGR9与人脐静脉内皮细胞有良好的体外结合能力。成功制备出肿瘤双靶点RGD10-NGR9-超顺磁性氧化铁,电镜观测近似圆球形,总粒径约30 nm。经振动样品磁强计仪测定,70℃时,复合粒子的饱和磁化强度为53.54 emu/g,无磁滞现象,有超顺磁性,Zeta电位－60.9 mV。结论 成功制备出RGD10-NGR9-超顺磁性氧化铁,其物理性质稳定,具有肿瘤血管生成靶向性。 |
| 英文摘要: |
| Objective To construct angiogenesis-specific RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles, and to observe the physical properties. Methods Dual-targeting peptides RGD10-NGR9 were designed and synthesized. Fluorescence labeled RGD10-NGR9 peptides were synthesized by incorporating flourescein iso-thiocyanate (FITC) into peptides. Human umbilical vein endothelia cells (HUVEC) were incubated with FITC labeled peptides and subsequently tested by inverted microscope. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with narrow size distribution having average diameters of 8—12 nm were synthesized by co-precipitation chemical method, and the surface was modified to be hydrophilic by coating with dextran. Then, dextran was oxidized and cross-linked to USPIO by propylene oxide, and the hybrid peptides RGD10-NGR9 were finally conjugated to the surface of USPIO in Schiff bases with dextran. The morphology of prepared nanoparticles was observed under electron microscope. The mean particle size and size distribution were observed by dynamic light scattering. The surface coating materials were determined by infrared spectrometer. Zeta potential was tested and magnetic intensity was examined by vibrating sample magnetometer. Results In vitro studies demonstrated a better binding affinity of FITC-RGD10-NGR9 to HUVEC. RGD10-NGR9 targeted USPIO nanoparticles were successfully constructed. The transmission electron microscopy of the nanoparticles was homogeneous in size and round in shape, with average diameters of 30 nm. The stable properties were tested with Zeta potential of -60.9 mV and magnetic intensity of 53.54 emu/g under 70℃. Conclusion RGD10-NGR9 targeted peptides have active targeting properties to tumor angiogenesis, with good affinity to HUVEC in vitro. The novel synthesized RGD10-NGR9-USPIO has stable properties. |
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