携Sialyl Lewis^x和抗ICAM-1单抗双配体微泡靶向黏附行为方式的体外研究  

Adhesive behavior of dual-targeted microbubbles carrying both Sialyl Lewisx and anti-ICAM-1 monoclonal antibody in vitro

作　　者：李美瑜[1] 杨莉[2] 吴爵非[1] 肖云彬[1] 宾建国[1] 刘莹[1] 宾建平[1] 

机构地区：[1]南方医科大学南方医院心内科,广州510515 [2]南方医科大学药学部

出　　处：《中华超声影像学杂志》2011年第2期168-171,共4页Chinese Journal of Ultrasonography

基　　金：国家“863”计划项目（2006AA022478）;国家自然科学基金（3087（1722）

摘　　要：目的 体外对比评价携Sialyl Lewisx和抗ICAM-1单抗双配体和同型对照单配体微泡的靶向黏附行为方式.方法 构建携Sialyl Lewisx与抗ICAM-1单抗双配体（MB-D）、携Sialyl Lewisx（MB-S）和抗ICAM-1单抗（MB-I）三种靶向微泡,利用平行板流动腔和Image-Pro-Plus图像分析软件,分别在0.6、2.0和4.0 dyn/cm2三种剪切应力下分析每种微泡流动过程的速度变化,测定滚动和牢固结合的微泡数目,并检测三种靶向微泡的半数解离应力.结果 0.6 dyn/cm2时单个视野内微泡的滚动数目,MB-D和MB-S明显高于MB-I（P＜0.05）,而在2.0和4.0 dyn/cm2时MB-S分别约是MB-D和MB-I的1.47～1.70倍和4.52～10.65倍（P＜0.05）.三种剪切应力下微泡的全程（6 min）结合数目MB-D分别为MB-S和MB-I的1.40～1.44倍和2.18～3.78倍（P＜0.05）.MB-S、MB-D和MB-I的半数解离应力依次递增.结论 三种微泡具有不同的靶向黏附行为方式,MB-I表现为低效滚动后的牢固结合,MB-S呈高效滚动后的不稳定黏附,而MB-D能够实现高效滚动后相对牢固的结合,其靶向黏附效能明显高于同型对照微泡,有望在体内动脉系统高剪切应力状态下实现分子影像评价.Objective To assess the adhesive behavior of dual-targeted microbubbles carrying both Sialyl Lewisx and anti-ICAM-1 monoclonal antibodies in vitro. Methods Selectin-targeted （with Sialyl Lewisx） microbubbles （MB-S）,ICAM-1-targeted （with anti-ICAM-1 monoclonal antibodies） microbubbles （MB-Ⅰ）,and dual-targeted （with both ligands） microbubbles（MB-D） were prepared by attaching the ligands to the biotinylated lipid-microbubbles via multi-step avidin biotin bridging chemistry. A parallel plate flow chamber combined with a novel automated tracking algorithm,were used to analyze the transient velocities,rolling and firmly adherent numbers of microbubbles at various shear stress （0. 6,2.0 and 4.0 dyn/cm2）over 6 min. Microbubbles detachments were tested by ramping up the shear stress at 30 s intervals. Results At 0.6 dyn/cm2 shear stress, the rolling numbers of MB-S and MB-D were remarkably more than that of MB-I（ P〈0.05）, while at 2.0 and 4.0 dyn/cm2 MB-S performed higher rolling efficiency as compared with either MB-I and MB-D （ P〈 0.05）. In all flow conditions, the adhesive numbers of MB-D to the targets were obviously greater than those of MB-S and MB-I （ P〈 0.05）. Half-maximal detachment decreased gradually in MB-I, MB-D and MB-S by turns （ P〈 0.05）. Conclusions MB-I, MB-S and MB-D have different adhesive behaviors. MB-I exhibites primarily firm adhesion with low rolling efficiency, while MB-S reveales unstable or transient adhesion with high rolling efficiency,and MB-D exhibites firm adhesion with high rolling efficiency. MB-D may be suitable for molecular imaging in high-flow vessels.

关 键 词：微气泡 基因打靶 平行板流动腔 黏附行为方式 

分 类 号：R310[医药卫生—基础医学]