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Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide
A key challenge in treating solid tumors is that the tumor microenvironment often inhibits the penetration of therapeutic antibodies into the tumor, leading to reduced therapeutic efficiency. It has been reported that the combination of ultrasound-responsive micro/nanobubble and therapeutic ultrasou...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861716/ https://www.ncbi.nlm.nih.gov/pubmed/36678759 http://dx.doi.org/10.3390/pharmaceutics15010130 |
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author | Yano, Yusuke Hamano, Nobuhito Haruta, Kenshin Kobayashi, Tomomi Sato, Masahiro Kikkawa, Yamato Endo-Takahashi, Yoko Tada, Rui Suzuki, Ryo Maruyama, Kazuo Nomizu, Motoyoshi Negishi, Yoichi |
author_facet | Yano, Yusuke Hamano, Nobuhito Haruta, Kenshin Kobayashi, Tomomi Sato, Masahiro Kikkawa, Yamato Endo-Takahashi, Yoko Tada, Rui Suzuki, Ryo Maruyama, Kazuo Nomizu, Motoyoshi Negishi, Yoichi |
author_sort | Yano, Yusuke |
collection | PubMed |
description | A key challenge in treating solid tumors is that the tumor microenvironment often inhibits the penetration of therapeutic antibodies into the tumor, leading to reduced therapeutic efficiency. It has been reported that the combination of ultrasound-responsive micro/nanobubble and therapeutic ultrasound (TUS) enhances the tissue permeability and increases the efficiency of delivery of macromolecular drugs to target tissues. In this study, to facilitate efficient therapeutic antibody delivery to tumors using this combination system, we developed therapeutic antibody-modified nanobubble (NBs) using an Fc-binding polypeptide that can quickly load antibodies to nanocarriers; since the polypeptide was derived from Protein G. TUS exposure to this Herceptin(®)-modified NBs (Her-NBs) was followed by evaluation of the antibody’s own ADCC activity, resulting the retained activity. Moreover, the utility of combining therapeutic antibody-modified NBs and TUS exposure as an antibody delivery system for cancer therapy was assessed in vivo. The Her-NBs + TUS group had a higher inhibitory effect than the Herceptin and Her-NBs groups. Overall, these results suggest that the combination of therapeutic antibody-modified NBs and TUS exposure can enable efficient antibody drug delivery to tumors, while retaining the original antibody activity. Hence, this system has the potential to maximize the therapeutic effects in antibody therapy for solid cancers. |
format | Online Article Text |
id | pubmed-9861716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98617162023-01-22 Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide Yano, Yusuke Hamano, Nobuhito Haruta, Kenshin Kobayashi, Tomomi Sato, Masahiro Kikkawa, Yamato Endo-Takahashi, Yoko Tada, Rui Suzuki, Ryo Maruyama, Kazuo Nomizu, Motoyoshi Negishi, Yoichi Pharmaceutics Article A key challenge in treating solid tumors is that the tumor microenvironment often inhibits the penetration of therapeutic antibodies into the tumor, leading to reduced therapeutic efficiency. It has been reported that the combination of ultrasound-responsive micro/nanobubble and therapeutic ultrasound (TUS) enhances the tissue permeability and increases the efficiency of delivery of macromolecular drugs to target tissues. In this study, to facilitate efficient therapeutic antibody delivery to tumors using this combination system, we developed therapeutic antibody-modified nanobubble (NBs) using an Fc-binding polypeptide that can quickly load antibodies to nanocarriers; since the polypeptide was derived from Protein G. TUS exposure to this Herceptin(®)-modified NBs (Her-NBs) was followed by evaluation of the antibody’s own ADCC activity, resulting the retained activity. Moreover, the utility of combining therapeutic antibody-modified NBs and TUS exposure as an antibody delivery system for cancer therapy was assessed in vivo. The Her-NBs + TUS group had a higher inhibitory effect than the Herceptin and Her-NBs groups. Overall, these results suggest that the combination of therapeutic antibody-modified NBs and TUS exposure can enable efficient antibody drug delivery to tumors, while retaining the original antibody activity. Hence, this system has the potential to maximize the therapeutic effects in antibody therapy for solid cancers. MDPI 2022-12-30 /pmc/articles/PMC9861716/ /pubmed/36678759 http://dx.doi.org/10.3390/pharmaceutics15010130 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yano, Yusuke Hamano, Nobuhito Haruta, Kenshin Kobayashi, Tomomi Sato, Masahiro Kikkawa, Yamato Endo-Takahashi, Yoko Tada, Rui Suzuki, Ryo Maruyama, Kazuo Nomizu, Motoyoshi Negishi, Yoichi Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title | Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title_full | Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title_fullStr | Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title_full_unstemmed | Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title_short | Development of an Antibody Delivery Method for Cancer Treatment by Combining Ultrasound with Therapeutic Antibody-Modified Nanobubbles Using Fc-Binding Polypeptide |
title_sort | development of an antibody delivery method for cancer treatment by combining ultrasound with therapeutic antibody-modified nanobubbles using fc-binding polypeptide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861716/ https://www.ncbi.nlm.nih.gov/pubmed/36678759 http://dx.doi.org/10.3390/pharmaceutics15010130 |
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