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Background: Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components., Methods: BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, 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 mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated., Results: This study indicated 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, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer., Conclusion: Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Interleukin-17A (IL-17A) is an important pro-inflammatory cytokine observed in the development of many disorders, such as psoriasis, rheumatoid arthritis, and multiple sclerosis. The anti-IL-17A biological drugs, including Secukinumab, Ixekizumab, and Brodalumab, are monoclonal antibodies approved for several disease treatments. Due to the disadvantages of biological therapies, including their immunogenicity, difficulties in scale generation, and high production costs and time, it is necessary to find new alternative anti- IL-17A agents for these monoclonal antibodies. Our study aimed to identify ssDNA aptamers that block IL-17A activity using the protein-SELEX procedure., Methods: The hIL-17A was expressed in codon plus E. coli, and after 14 rounds of the SELEX process, monitoring of aptamer pools was done using the dot blot method. Three families of aptamers were obtained from the selected round 9 aptamer pool, and seven truncates were created. Inhibitory effects of aptamer truncate on IL-17-induced CCL20 expression in HaCaT keratinocytes were evaluated., Results: All aptamer truncates had a significant inhibitory effect compared to the library, but the inhibitory effect of M2 and M7 truncates was more than 80%. Moreover, we evaluated the potential binding site of selected aptamers by ELISA., Conclusions: We introduced a new small 17-nucleotide DNA aptamer that efficiently binds and blocks hIL-17A with a 0.3 nM kd, a potential anti-IL-17A therapeutic agent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mojtaba Sankian reports financial support was provided by Mashhad University of Medical Sciences., (Copyright © 2022 Elsevier Inc. All rights reserved.)