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Article

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

1
Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
2
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan
3
Laboratory of Drug and Gene Delivery Research, Faculty of Pharma-Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
4
Graduate School of Science and Engineering, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 20 April 2019 / Revised: 10 June 2019 / Accepted: 12 June 2019 / Published: 15 June 2019
(This article belongs to the Special Issue Micro/Nano-Bubbles as a New Ultrasound Imaging and Drug Delivery Tool)
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. View Full-Text
Keywords: antibody-modified nanoparticles; nanobubbles; Fc-region-binding polypeptide; ultrasound tumor imaging antibody-modified nanoparticles; nanobubbles; Fc-region-binding polypeptide; ultrasound tumor imaging
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MDPI and ACS Style

Hamano, N.; Kamoshida, S.; Kikkawa, Y.; Yano, Y.; Kobayashi, T.; Endo-Takahashi, Y.; Suzuki, R.; Maruyama, K.; Ito, Y.; Nomizu, M.; Negishi, Y. Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging. Pharmaceutics 2019, 11, 283. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11060283

AMA Style

Hamano N, Kamoshida S, Kikkawa Y, Yano Y, Kobayashi T, Endo-Takahashi Y, Suzuki R, Maruyama K, Ito Y, Nomizu M, Negishi Y. Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging. Pharmaceutics. 2019; 11(6):283. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11060283

Chicago/Turabian Style

Hamano, Nobuhito, Sho Kamoshida, Yamato Kikkawa, Yusuke Yano, Tomomi Kobayashi, Yoko Endo-Takahashi, Ryo Suzuki, Kazuo Maruyama, Yuji Ito, Motoyoshi Nomizu, and Yoichi Negishi. 2019. "Development of Antibody-Modified Nanobubbles Using Fc-Region-Binding Polypeptides for Ultrasound Imaging" Pharmaceutics 11, no. 6: 283. https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11060283

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