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A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting
Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant pr...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403696/ https://www.ncbi.nlm.nih.gov/pubmed/25926731 http://dx.doi.org/10.2147/IJN.S77268 |
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author | Wang, Shan-Mei He, Xian Li, Nan Yu, Feng Hu, Yang Wang, Liu-Sheng Zhang, Peng Du, Yu-Kui Du, Shan-Shan Yin, Zhao-Fang Wei, Ya-Ru Mulet, Xavier Coia, Greg Weng, Dong He, Jian-Hua Wu, Min Li, Hui-Ping |
author_facet | Wang, Shan-Mei He, Xian Li, Nan Yu, Feng Hu, Yang Wang, Liu-Sheng Zhang, Peng Du, Yu-Kui Du, Shan-Shan Yin, Zhao-Fang Wei, Ya-Ru Mulet, Xavier Coia, Greg Weng, Dong He, Jian-Hua Wu, Min Li, Hui-Ping |
author_sort | Wang, Shan-Mei |
collection | PubMed |
description | Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery. |
format | Online Article Text |
id | pubmed-4403696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44036962015-04-29 A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting Wang, Shan-Mei He, Xian Li, Nan Yu, Feng Hu, Yang Wang, Liu-Sheng Zhang, Peng Du, Yu-Kui Du, Shan-Shan Yin, Zhao-Fang Wei, Ya-Ru Mulet, Xavier Coia, Greg Weng, Dong He, Jian-Hua Wu, Min Li, Hui-Ping Int J Nanomedicine Original Research Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery. Dove Medical Press 2015-04-13 /pmc/articles/PMC4403696/ /pubmed/25926731 http://dx.doi.org/10.2147/IJN.S77268 Text en © 2015 Wang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Wang, Shan-Mei He, Xian Li, Nan Yu, Feng Hu, Yang Wang, Liu-Sheng Zhang, Peng Du, Yu-Kui Du, Shan-Shan Yin, Zhao-Fang Wei, Ya-Ru Mulet, Xavier Coia, Greg Weng, Dong He, Jian-Hua Wu, Min Li, Hui-Ping A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title | A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title_full | A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title_fullStr | A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title_full_unstemmed | A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title_short | A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
title_sort | novel nanobody specific for respiratory surfactant protein a has potential for lung targeting |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403696/ https://www.ncbi.nlm.nih.gov/pubmed/25926731 http://dx.doi.org/10.2147/IJN.S77268 |
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