Identification of a nanobody specific to human pulmonary surfactant protein A
Abstract Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously construct...
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Nature Portfolio
2017
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oai:doaj.org-article:2dfa83ef24744015bf52012dcd4558452021-12-02T12:30:19ZIdentification of a nanobody specific to human pulmonary surfactant protein A10.1038/s41598-017-01456-22045-2322https://doaj.org/article/2dfa83ef24744015bf52012dcd4558452017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01456-2https://doaj.org/toc/2045-2322Abstract Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10−7 M. Nb4 (19 kDa) was stable at 30 °C–37 °C and pH 7.0–7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn’t react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn’t cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung.Xian HeShan-Mei WangZhao Fang YinMeng-Meng ZhaoNan LiFeng YuLiu-Sheng WangYang HuYu-Kui DuShan-Shan DuYan LiYa-Ru WeiShan-Shan ChenJian-Hua HeDong WengHui-Ping LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Xian He Shan-Mei Wang Zhao Fang Yin Meng-Meng Zhao Nan Li Feng Yu Liu-Sheng Wang Yang Hu Yu-Kui Du Shan-Shan Du Yan Li Ya-Ru Wei Shan-Shan Chen Jian-Hua He Dong Weng Hui-Ping Li Identification of a nanobody specific to human pulmonary surfactant protein A |
| description |
Abstract Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10−7 M. Nb4 (19 kDa) was stable at 30 °C–37 °C and pH 7.0–7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn’t react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn’t cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung. |
| format |
article |
| author |
Xian He Shan-Mei Wang Zhao Fang Yin Meng-Meng Zhao Nan Li Feng Yu Liu-Sheng Wang Yang Hu Yu-Kui Du Shan-Shan Du Yan Li Ya-Ru Wei Shan-Shan Chen Jian-Hua He Dong Weng Hui-Ping Li |
| author_facet |
Xian He Shan-Mei Wang Zhao Fang Yin Meng-Meng Zhao Nan Li Feng Yu Liu-Sheng Wang Yang Hu Yu-Kui Du Shan-Shan Du Yan Li Ya-Ru Wei Shan-Shan Chen Jian-Hua He Dong Weng Hui-Ping Li |
| author_sort |
Xian He |
| title |
Identification of a nanobody specific to human pulmonary surfactant protein A |
| title_short |
Identification of a nanobody specific to human pulmonary surfactant protein A |
| title_full |
Identification of a nanobody specific to human pulmonary surfactant protein A |
| title_fullStr |
Identification of a nanobody specific to human pulmonary surfactant protein A |
| title_full_unstemmed |
Identification of a nanobody specific to human pulmonary surfactant protein A |
| title_sort |
identification of a nanobody specific to human pulmonary surfactant protein a |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/2dfa83ef24744015bf52012dcd455845 |
| work_keys_str_mv |
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| _version_ |
1718394388211564544 |