An epicutaneous therapeutic pollen-allergen extract delivery system in the allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds

Abstract

Abstract Background: We investigated whether gold nanoparticles (GNPs) and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) could be effective for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and nonallergenic components. Methods: BALB/c mice were sensitized to total protein extract of Platanus orientalis pollen and then epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, the total extract loaded GNPs, and the total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). We then examined the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and the mixture of its recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue. Results: The current study showed that the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, histopathological analysis of lung tissue showed that it also led to a remarkable decrease in allergic rhinitis (AR)-associated inflammation and histopathological damage. The DC-targeted group showed greatest improvement in AR-related immune factors and had no histopathological damage compared with the same dose without aptamer. Conclusion: Consequently, it seems that loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in pollen-induced AR.