携Gelsolin单抗靶向相变型超声造影剂的制备及体外靶向实验  

Preparation of Gelsolin-targeted Phase Transition Ultrasound Contrast Agent and in Vitro Experiment

作　　者：杨燕 武俊[1] 秦颢诚 周盟[1] 张宇虹[1] 宋宇[1] 冉海涛[2] 

机构地区：[1]大连医科大学附属第二医院超声科,辽宁省大连市116027 [2]重庆医科大学附属第二医院超声科

出　　处：《中国超声医学杂志》2017年第10期936-939,共4页Chinese Journal of Ultrasound in Medicine

基　　金：国家自然基金项目(No.81501476);辽宁省自然基金项目(No.2014023001)

摘　　要：目的制备一种以凝溶胶蛋白(GSN)为靶点的包裹液态氟碳的纳米级PLGA高分子造影剂(GSN-PLGA-PFP),并评价其体外热致相变、靶向及显影能力。方法采用双乳化法及碳二亚胺法制备靶向相变型高分子超声造影剂。检测此造影剂的一般性质;显微镜加热板法进行热致相变;激光共聚焦显微镜体外观察GSN-PLGA-PFP被小鼠腹水型肝癌高淋巴道转移Hca-F细胞摄取的情况,初步评价其寻靶能力;体外低强度聚焦超声(LIFU)仪辐照后观察其超声显影效果。结果 GSN-PLGA-PFP的平均粒径为(328.59±3.82)nm,造影剂表面平均Zeta电位为(-10.36±1.34)mV,造影剂表面GSN单抗连接率高达98.31%,且于43.5℃时纳米粒开始发生相变;体外摄取实验显示Hca-F细胞可较多地摄取GSNPLGA-PFP,体外行LIFU辐照后可观察到显影效果明显增强。结论自制携Gelsolin单抗包载PFP的PLGA造影剂热致相变效果明显,可与Hca-F细胞特异度结合且体外显影效果较好。Objective To prepare a kind o{ Gelsohn-targeted ultrasound contrast agent with liquid perfluocarbon （GSN-PLGA-PFP） for heat and ultrasound induced droplet to-bubble transition and explore its targeting in vitro. Methods The high molecular ultrasound contrast agent were prepared by a modified double emulsion technique and then conjugated with Gelsolin monoclonal antibody by carbodiimide technique. The physical property was observed by light microscope and Malvern laser detector. The phase-change of nano-emulsions was evaluated by heat and low inten- sity focused ultrasound. Laser eonfoeal microscope was used to assess the binding of ultrasound contrast agents to Hca- F cells. Results The average diameter of GSN-PLGA-PFP was （828.59 ~ 3.82） nm, the potential was （--10.36 ＋ 1.34） mV and the binding rate of Gelsolin monoclonal antibody was as high as 98.31%. When heating at 43.5 ℃ ,the phase change of nano-emulsions had just begun. In vitro experiment showed that the Hca-F can intake more GSN-PL- GA-PFP. Conclusions The GSN-PLGA-PFP can bind to Hca-F cells specifically and with excellent phase transition which make it can enhance the ultrasound imaging greatly.

关 键 词：聚乳酸羟基乙酸 GELSOLIN 相变 靶向超声造影剂 

分 类 号：R981[医药卫生—药品]