A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting
Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of M...
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Dove Medical Press
2015
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oai:doaj.org-article:da8b57f3da4a46b28248a5c56e30ddd12021-12-02T00:31:21ZA novel nanobody specific for respiratory surfactant protein A has potential for lung targeting1178-2013https://doaj.org/article/da8b57f3da4a46b28248a5c56e30ddd12015-04-01T00:00:00Zhttp://www.dovepress.com/a-novel-nanobody-specific-for-respiratory-surfactant-protein-a-has-pot-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 2School of Medicine, Suzhou University, SuZhou, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 4Department of Chest Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5CSIRO (Commonwealth Scientific and Industrial Research) Materials Science and Engineering, Clayton, 6CSIRO Materials Science and Engineering, Parkville, Melbourne, VIC, Australia; 7Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA *These authors contributed equally to this work Abstract: 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. Keywords: nanobodies, rSPA, phage-nanobody library, VHH, lung-targeting drugsWang SMHe XLi NYu FHu YWang LSZhang PDu YKDu SSYin ZFWei YRMulet XCoia GWeng DHe JHWu MLi HPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2857-2869 (2015) |
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DOAJ |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Wang SM He X Li N Yu F Hu Y Wang LS Zhang P Du YK Du SS Yin ZF Wei YR Mulet X Coia G Weng D He JH Wu M Li HP A novel nanobody specific for respiratory surfactant protein A has potential for lung targeting |
| description |
Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 2School of Medicine, Suzhou University, SuZhou, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 4Department of Chest Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5CSIRO (Commonwealth Scientific and Industrial Research) Materials Science and Engineering, Clayton, 6CSIRO Materials Science and Engineering, Parkville, Melbourne, VIC, Australia; 7Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA *These authors contributed equally to this work Abstract: 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. Keywords: nanobodies, rSPA, phage-nanobody library, VHH, lung-targeting drugs |
| format |
article |
| author |
Wang SM He X Li N Yu F Hu Y Wang LS Zhang P Du YK Du SS Yin ZF Wei YR Mulet X Coia G Weng D He JH Wu M Li HP |
| author_facet |
Wang SM He X Li N Yu F Hu Y Wang LS Zhang P Du YK Du SS Yin ZF Wei YR Mulet X Coia G Weng D He JH Wu M Li HP |
| author_sort |
Wang SM |
| title |
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_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_sort |
novel nanobody specific for respiratory surfactant protein a has potential for lung targeting |
| publisher |
Dove Medical Press |
| publishDate |
2015 |
| url |
https://doaj.org/article/da8b57f3da4a46b28248a5c56e30ddd1 |
| work_keys_str_mv |
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