A LIPOPEPTIDE-BASED αVβ3 INTEGRIN-TARGETED ULTRASOUND CONTRAST AGENT FOR MOLECULAR IMAGING OF TUMOR ANGIOGENESIS
A LIPOPEPTIDE-BASED αVβ3 INTEGRIN-TARGETED ULTRASOUND CONTRAST AGENT FOR MOLECULAR IMAGING OF TUMOR ANGIOGENESIS
复制标题
基于脂肽的 alphavbeta(3) 整合素靶向超声造影剂用于肿瘤血管生成的分子成像
DOI：
10.1016/j.ultrasmedbio.2015.05.023
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发表时间：
2015-10-01
影响因子：
2.9
通讯作者：
Zheng, Hairong
中科院分区：
文献类型：
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作者：
Yan, Fei;Xu, Xiuxia;Zheng, Hairong
靶向超声造影剂的设计和制造是超声分子成像应用成功的关键因素。在这里，我们通过将iRGD-脂肽掺入MB膜中引入可转化的α v β（3）整合素靶向微泡（MB），用于肿瘤血管生成的非侵入性超声成像。首先，通过将iRGD肽缀合至二硬脂酰-磷脂酰乙醇胺-聚乙二醇2000-马来酰亚胺来合成iRGD-脂肽。所得iRGD-脂肽用于制备携带iRGD的α v β（3）整联蛋白靶向MB（iRGD-MB）。在体外静态和动态条件下，发现iRGDMB对内皮细胞的结合特异性显著强于对照MB（p < 0.01）。iRGD-MB在内皮细胞上的结合通过与抗α v或抗β（3）抗体预孵育而被竞争消除（p < 0.01）。在静脉注射iRGD-MB或对照MB后，对携带4 T1乳腺肿瘤的小鼠进行超声成像，显示iRGD-MB的肿瘤内存在强烈的对比度增强，但对照MB没有; iRGD-MB的平均声学信号强度为10.71 +/- 2.75强度单位，对照MB为1.13 +/- 0.18强度单位（p，0.01）。免疫荧光染色证实α v β 3整合素的存在。这些数据表明，iRGD-MB可以用作超声成像探针，用于肿瘤血管生成的非侵入性分子成像，并可能对超声图像引导的肿瘤靶向药物递送具有进一步的影响。（E-mail：lmeihong@fimmu.com or hr. siat.ac.cn）（C）2015年世界医学与生物学超声联合会。
The design and fabrication of targeted ultrasound contrast agents are key factors in the success of ultrasound molecular imaging applications. Here, we introduce a transformable alpha v beta(3) integrin-targeted microbubble (MB) by incorporation of iRGD-lipopeptides into the MB membrane for non-invasive ultrasound imaging of tumor angiogenesis. First, the iRGD-lipopeptides were synthesized by conjugating iRGD peptides to distearoyl-phosphatidylethanolamine-polyethylene glycol 2000-maleimide. The resulting iRGD-lipopeptides were used for fabrication of the iRGD-carrying alpha v beta(3) integrin-targeted MBs (iRGD-MBs). The binding specificity of iRGDMBs for endothelial cells was found to be significantly stronger than that of control MBs (p < 0.01) under in vitro static and dynamic conditions. The binding of iRGD-MBs on the endothelial cells was competed off by pre-incubation with the anti-alpha v or anti-beta(3) antibody (p < 0.01). Ultrasound images taken of mice bearing 4T1 breast tumors after intravenous injections of iRGD-MBs or control MBs revealed strong contrast enhancement within the tumors from iRGD-MBs but not from the control MBs; the mean acoustic signal intensity was 10.71 +/- 2.75 intensity units for iRGD-MBs versus 1.13 +/- 0.18 intensity units for the control MBs (p, 0.01). The presence of alpha v beta(3) integrin was confirmed by immunofluorescence staining. These data indicate that iRGD-MBs can be used as an ultrasound imaging probe for the non-invasive molecular imaging of tumor angiogenesis, and may have further implications for ultrasound image-guided tumor targeting drug delivery. (E-mail: lmeihong@fimmu.com or hr.zheng@siat.ac.cn) (C) 2015 World Federation for Ultrasound in Medicine & Biology.