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Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging

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 si...

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Autores principales: Hamano, Nobuhito, Kamoshida, Sho, Kikkawa, Yamato, Yano, Yusuke, Kobayashi, Tomomi, Endo-Takahashi, Yoko, Suzuki, Ryo, Maruyama, Kazuo, Ito, Yuji, Nomizu, Motoyoshi, Negishi, Yoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631014/
https://www.ncbi.nlm.nih.gov/pubmed/31208098
http://dx.doi.org/10.3390/pharmaceutics11060283
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author Hamano, Nobuhito
Kamoshida, Sho
Kikkawa, Yamato
Yano, Yusuke
Kobayashi, Tomomi
Endo-Takahashi, Yoko
Suzuki, Ryo
Maruyama, Kazuo
Ito, Yuji
Nomizu, Motoyoshi
Negishi, Yoichi
author_facet Hamano, Nobuhito
Kamoshida, Sho
Kikkawa, Yamato
Yano, Yusuke
Kobayashi, Tomomi
Endo-Takahashi, Yoko
Suzuki, Ryo
Maruyama, Kazuo
Ito, Yuji
Nomizu, Motoyoshi
Negishi, Yoichi
author_sort Hamano, Nobuhito
collection PubMed
description 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.
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spelling pubmed-66310142019-08-19 Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging Hamano, Nobuhito Kamoshida, Sho Kikkawa, Yamato Yano, Yusuke Kobayashi, Tomomi Endo-Takahashi, Yoko Suzuki, Ryo Maruyama, Kazuo Ito, Yuji Nomizu, Motoyoshi Negishi, Yoichi Pharmaceutics Article 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. MDPI 2019-06-15 /pmc/articles/PMC6631014/ /pubmed/31208098 http://dx.doi.org/10.3390/pharmaceutics11060283 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamano, Nobuhito
Kamoshida, Sho
Kikkawa, Yamato
Yano, Yusuke
Kobayashi, Tomomi
Endo-Takahashi, Yoko
Suzuki, Ryo
Maruyama, Kazuo
Ito, Yuji
Nomizu, Motoyoshi
Negishi, Yoichi
Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title_full Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title_fullStr Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title_full_unstemmed Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title_short Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging
title_sort development of antibody-modified nanobubbles using fc-region-binding polypeptides for ultrasound imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631014/
https://www.ncbi.nlm.nih.gov/pubmed/31208098
http://dx.doi.org/10.3390/pharmaceutics11060283
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