Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
复制标题
DOI：
10.3390/pharmaceutics11060283
复制
发表时间：
2019-06-01
期刊：
影响因子：
5.4
通讯作者：
Negishi, Yoichi
中科院分区：
文献类型：
--
作者：
Hamano, Nobuhito;Kamoshida, Sho;Negishi, Yoichi
超声（US）成像是一种广泛使用的成像技术。使用超声造影剂，如微泡，它由磷脂组成，并充满了全氟化碳气体，已成为临床超声成像的一个不可或缺的组成部分，而分子超声成像最近吸引了显着的关注与有效的诊断相结合。抗生物素蛋白-生物素相互作用方法经常用于将抗体拴系到微泡，从而导致分子靶向US成像剂的开发。然而，抗生物素蛋白仍有局限性，如免疫原性。我们以前报道过，含有全氟化碳气体的脂质纳米气泡（NB）适用于US成像和基因递送。在本文中，我们报告了一种新的抗体修饰方法的开发使用Fc区结合多肽衍生自蛋白A/G的NB。首先，我们使用该多肽制备了抗CD 146抗体修饰的NB，导致与表达CD 146的人脐静脉内皮细胞的高水平附着。为了检查它们的靶向能力和US成像能力，将NB施用于荷瘤小鼠。与未标记的NB相比，抗体修饰的NB的对比度成像被证明是延长的。因此，这种使用Fc结合多肽的抗体修饰方法可能是开发下一代抗体修饰的US成像剂的可行工具。
Ultrasound (US) imaging is a widely used imaging technique. The use of US contrast agents such as microbubbles, which consist of phospholipids and are filled with perfluorocarbon gases, has become an indispensable component of clinical US imaging, while molecular US imaging has recently attracted significant attention in combination with efficient diagnostics. The avidin-biotin interaction method is frequently used to tether antibodies to microbubbles, leading to the development of a molecular targeting US imaging agent. However, avidin still has limitations such as immunogenicity. We previously reported that lipid-based nanobubbles (NBs) containing perfluorocarbon gas are suitable for US imaging and gene delivery. In this paper, we report on the development of a novel antibody modification method for NBs using Fc-region-binding polypeptides derived from protein A/G. First, we prepared anti-CD146 antibody-modified NBs using this polypeptide, resulting in high levels of attachment to human umbilical vein endothelial cells expressing CD146. To examine their targeting ability and US imaging capability, the NBs were administered to tumor-bearing mice. The contrast imaging of antibody-modified NBs was shown to be prolonged compared with that of non-labeled NBs. Thus, this antibody modification method using an Fc-binding polypeptide may be a feasible tool for developing a next-generation antibody-modified US imaging agent.