上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

携抗VEGFR2抗体PLGA靶向超声造影剂的制备及体外寻靶实验

王翠薇1，杜 晶1，杨仕平2，胡 鹤2，李凤华1   

  1. 1.上海交通大学 医学院附属仁济医院超声医学科， 上海 200127； 2.上海师范大学化学系， 上海 200234
  • 出版日期:2014-06-28 发布日期:2014-06-30
  • 通讯作者: 李凤华, 电子信箱: fenghua-li@163.com。
  • 作者简介:王翠薇（1988—）， 女， 硕士生; 电子信箱: cwwang0510@163.com。
  • 基金资助:

    国家自然科学基金（81102014）

Preparation of VEGFR2-targeted PLGA ultrasound contrast agent and in vitro targeting tests

WANG Cui-wei1, DU Jing1, YANG Shi-ping2, HU He2, LI Feng-hua1   

  1. 1.Department of Ultrasound, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2.Department of Chemistry, Shanghai Normal University, Shanghai 200234, China
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    National Natural Science Foundation of China, 81102014

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摘要：

目的 制备携抗血管内皮细胞生长因子受体2（VEGFR2）抗体聚乳酸羟基乙酸（PLGA）靶向超声造影剂，并考察其体外寻靶能力与超声显像性能。方法 通过改进的双乳化溶剂挥发法制备高分子材料PLGA纳米粒子，利用扫描电子显微镜对其一般特性进行表征，并进一步用碳二亚胺法将造影剂与抗VEGFR2抗体耦联制备靶向超声造影剂，使用激光共聚焦扫描显微镜对其体外寻靶能力进行初步评估，使用高频超声诊断仪观察体外显像效果。结果 PLGA超声造影剂粒子呈规则球形、大小均一、分散性好；在体外寻靶实验中，携抗VEGFR2抗体PLGA靶向造影剂能够较多并牢固的聚集到血管肉瘤内皮细胞(SVR)表面；体外超声成像实验中，携抗VEGFR2抗体PLGA靶向超声造影剂呈点状细密高回声，后方回声无衰减。结论 本研究成功制备携抗VEGFR2抗体PLGA靶向超声造影剂，能够在体外与VEGFR2高表达的血管肉瘤内皮细胞特异性靶向结合，且体外超声显像效果良好。

关键词: 聚乳酸羟基乙酸, 纳米粒子, 靶向超声造影剂, 血管内皮细胞生长因子受体2

Abstract:

Objective To prepare the poly lactic-co-glycolic acid (PLGA) vascular endothelial growth factor receptor 2 (VEGFR2)-targeted ultrasound contrast agent and observe its targeting and imaging ability in vitro. Methods The PLGA nanoparticles (NPs) of macromolecule material were prepared by a modified double-emulsion solvent evaporation method. General properties of PLGA NPs were detected by the FE SEM. The contrast agent and anti-VEGFR2 antibody were conjugated to prepare the targeted ultrasound contrast agent by the carbodiimide method. The LSCM was used to evaluate the targeting ability in vitro and the high frequency ultrasonography was used to observe the imaging ability in vitro. Results NPs of PLGA ultrasound contrast agent were regularly round with uniform size and good dispersion. The PLGA VEGFR2-targeted ultrasound contrast agent firmly attached to the surface of SVEN1 ras (SVR) during the course of targeting tests in vitro. The in vitro ultrasound imaging of the PLGA VEGFR2-targeted ultrasound contrast agent showed fine punctuate hyper echo with no attenuation for the rear echo. Conclusion The PLGA VEGFR2-targeted ultrasound contrast agent is prepared successfully. It can specifically target and attach to SVR with high expression of VEGFR2 in vitro and its in vitro ultrasound imaging is good.

Key words: poly lactic-co-glycolic acid, nanoparticles, targeted ultrasound contrast agent, vascular endothelial growth factor receptor 2