A stimulus-responsive contrast agent for ultrasound molecular imaging
A stimulus-responsive contrast agent for ultrasound molecular imaging
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DOI：
10.1016/j.biomaterials.2007.10.011
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发表时间：
2008-02-01
期刊：
影响因子：
14
通讯作者：
Ferrara, Katherine W.
中科院分区：
文献类型：
--
作者：
Borden, Mark A.;Zhang, Hua;Ferrara, Katherine W.
靶向配体的补体激活是控制分子成像靶向胶体造影剂命运的一个重要问题。在这里，我们扩展了之前对刺激响应微泡结构的研究，其中配体通常被聚合物刷子埋藏并通过超声辐射力瞬时显露，以显示使用生理肽配体减少补体激活和集中粘附到细胞。与传统的暴露配体基序和无配体对照相比，埋藏配体结构的体外 C3/C3b 附着以及体外和体内可溶性 C3a 过敏毒素的产生显着降低。此外，当在静态室中受浮力驱动时，埋入配体结构可防止携带精氨酸-甘氨酸-酪氨酸（RGD）的微泡与表达整合素的人脐静脉内皮细胞（HUVEC）粘附，但当被超声辐射力脉冲激活时，它不会影响粘附效率。这些结果首次表明了埋藏配体结构降低免疫原性的分子机制以及使用生理配体-受体对靶向该基序的可行性。 (c) 2007 Elsevier Ltd. 保留所有权利。
Complement activation by targeting ligands is an important issue that governs the fate of targeted colloidal contrast agents for molecular imaging. Here, we extend previous work on a stimulus-responsive microbubble construct, in which the ligand is normally buried by a polymeric overbrush and transiently revealed by ultrasound radiation force, to show reduced complement activation and focused adhesion to cells using a physiological peptide ligand. Attachment of C3/C3b in vitro and production of soluble C3a anaphylotoxin in vitro and in vivo decreased significantly for the buried-ligand architecture vs. the conventional exposed-ligand motif and no-ligand control. Additionally, the buried-ligand architecture prevented adhesion of Arg-Gly-Tyr (RGD)-bearing microbubbles to integrin-expressing human umbilical vein endothelial cells (HUVEC) when driven by buoyancy in a static chamber, but it did not affect adhesion efficiency when activated by ultrasound radiation force pulses. These results show, for the first time, the molecular mechanism for reduced immunogenicity for the buried-ligand architecture and feasibility of targeting with this motif using a physiological ligand-receptor pair. (c) 2007 Elsevier Ltd. All rights reserved.