Title
A Novel Nanobody Specific for Respiratory Surfactant Protein A has Potential for Lung Targeting
Document Type
Article
Publication Date
4-15-2015
Publication Title
International Journal of Nanomedicine
Volume
10
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.
First Page
2857
Last Page
2869
DOI
10.2147/IJN.S77268
ISSN
11769114
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Recommended Citation
Shan-Mei Wang, Xian He, Nan Li, et al.. "A Novel Nanobody Specific for Respiratory Surfactant Protein A has Potential for Lung Targeting" (2015). Biomedical Sciences Faculty Publications. 8.
https://commons.und.edu/bms-fac/8