携RGDS超声造影剂的制备及体外靶向血栓研究  

Targeting RGDS-mediated liposome ultrasound contrast agent: preparation and preliminary in vitro study

作　　者：杨钰楠[1] 高云华[1] 谭开彬[1] 夏红梅[1] 刘政[1] 李馨[1] 

机构地区：[1]第三军医大学新桥医院超声科,重庆400037

出　　处：《第三军医大学学报》2006年第6期562-564,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目(30500478);重庆市科技计划项目(2004AC5040)~~

摘　　要：目的探讨制备携精氨酸-甘氨酸-天冬氨酸-丝氨酸(Arg-G ly-Asp-Ser,RGDS)靶向脂膜超声造影剂的制备,并对靶向微泡的特性及靶向作用进行初步鉴定。方法分别采用酰胺键共价键合的方式和表面吸附法将脂膜超声造影剂与RGDS血栓靶向短肽片段进行结合;制备产物通过流式细胞仪进行携带率和稳定性的检测;对内源性凝血途径产生的血栓进行寻靶作用研究。结果流式细胞仪显示共价键合RGDS脂膜超声造影剂其微泡外壳波长发生了明显变化,显示改变率达到82%,而表面吸附法制备的靶向超声造影剂改变率达到23%;激光共聚焦显微镜显示携带RGDS的脂膜超声造影剂在大量的PBS液清洗后,对离体血栓仍具有很强的靶向性和稳定性,而表面吸附法制备的靶向超声造影剂在大量PBS液清洗后,失去了其靶向性。结论采用共价键合的化学修饰方法可以成功制备稳定性好的亲血栓靶向脂膜超声造影剂。Objective To discuss the preparation and preliminary in vitro study of the targeting RGDS-mediated liposome ultrasound contrast agent and investigate their biological properties. Methods Liposome ultrasound contrast agent combined with thrombus-targeted peptide RGDS through two methods, one is by amide linkage, the other one by surface bind. The conjunct ratio and stability were accessed by flow cytometer （ FCM）, the targeting effect of the targeted contrast agent on the thrombus was evaluated by intrinsic coagulation path. Results FCM demonstrated that the first method made the shell＇ s wavelength of targeted liposome microbubbles changed greatly and its conjunct ratio achieved 82%, while the conjunct ratio achieved 23% by the second method. Confocal scanning laser microscopy showed the priority of RGDS-mediated liposome ultrasound contrast agent by amide linkage in targeting and stability on grafted thrombus after repeated wash, but the targeted microbubbles through surface binding lost its targeting after repeated wash. Conclusion The thrombus-targeted liposome microbubbles combined with peptide by amide linkage were prepared successfully.

关 键 词：RGDS 血栓 靶向造影剂 体外靶向血栓 表面吸附法 

分 类 号：R445.1[医药卫生—影像医学与核医学] R965[医药卫生—诊断学]