| 李美瑜,肖云彬,宾建国,吴爵非,杨莉,胡广全,刘莹,黄瑞珠,宾建平.体外评价携Sialyl Lewisx和抗ICAM-1单抗双配体超声微泡的靶向黏附性能[J].中国医学影像技术,2010,26(7):1209~1213 |
| 体外评价携Sialyl Lewisx和抗ICAM-1单抗双配体超声微泡的靶向黏附性能 |
| In vitro evaluation of targeting capability of dual-targeted microbubbles carrying both Sialyl Lewisx and anti-ICAM-1 monoclonal antibody |
| 投稿时间：2009-12-16 最后修改时间：2010-1-21 |
| DOI： |
| 中文关键词: 微泡 造影剂 平行板流动腔 Sialyl Lewisx 细胞间黏附分子-1 |
| 英文关键词:Microbubbles Contrast media Parallel plate flow chamber Sialyl Lewisx Intercellular adhesion molecule-1 |
| 基金项目:国家863计划项目(2006AA02Z478)、国家自然科学基金(30870722)。 |
|
| 摘要点击次数: 67 |
| 全文下载次数: 29 |
| 中文摘要: |
| 目的 构建携Sialyl Lewisx和抗ICAM-1单抗双配体和同型对照单配体靶向超声微泡,体外对比评价其靶向黏附性能。 方法 采用"亲和素-生物素"桥接法构建携Sialyl Lewisx与抗ICAM-1单抗双配体(MB-D)、携Sialyl Lewisx(MB-S)和携抗ICAM-1单抗(MB-I)三种靶向超声微泡,以流式细胞术定量分析其配体结合率,并利用平行板流动腔分别在0.5、2.0和4.0 dyn/cm2三种剪切应力下的不同时间点观察微泡的结合及解离情况。 结果 MB-D、MB-S和MB-I的配体结合率均达85%以上,各组间无统计学差异(P>0.05)。在三种剪切应力下,MB-D和MB-S集中于前3~5 min高效结合,在5 min后两者的结合率均呈平台状态,而MB-I全程结合率(1~6 min)均呈低水平状态;MB-D的平均结合率和全程结合数目均明显高于MB-S和MB-I(P<0.05),而半数解离剪切应力则按MB-I、MB-D和MB-S顺序依次递减(P<0.05)。 结论 相同条件下,MB-S表现为早期快速、不稳定的黏附,MB-I为缓慢、牢固的结合,而MB-D呈早期高效、相对牢固的结合。MB-D有可能用于高流速的动脉超声分子成像。 |
| 英文摘要: |
| Objective To synthesize dual-targeted microbubbles carrying both Sialyl Lewisx and anti-ICAM-1 monoclonal antibodies, and to assess their binding capability to targets in vitro. Methods Dual-targeted (via both targeting ligands) microbubbles (MB-D) selectin-targeted (via Sialyl Lewisx) microbubbles (MB-S) and ICAM-1-targeted (via anti-ICAM-1 monoclonal antibodies) microbubbles (MB-I) were prepared with attaching the ligands to the biotinylated lipid-microbubbles via multi-step avidin biotin bridging chemistry. The binding rate of ligands in microbubbles was measured with quantitative flow cytometry. A parallel plate flow chamber was used to determine the targeting efficiency of the microbubbles at various shear stress (0.5, 2.0 and 4.0 dyn/cm2) over 6 min. And microbubbles detachments were tested by ramping up the shear stress at 30 s intervals. Results All of the ligand-binding rates in MB-D, MB-S and MB-I were more than 85% (P>0.05). In all flow conditions, the adhesive numbers of MB-D and MB-S to the targets increased rapidly in the first 3—5 min, followed by a plateau, while the adhesive number of MB-I increased very low in the whole course. The adhesive number and mean adhesive rate of MB-D 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). Conclusion In the same condition, MB-S has a rapid and instability binding capability in the early stage, MB-I has a slow and firm binding capability. MB-D has a rapid and firm binding capability to the specific targets. MB-D can be used to achieve ultrasound molecular imaging in high-shear floor. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|