Introduction Interleukin‐17 (IL17) plays a crucial role in the development of psoriatic plaques, making it a valuable therapeutic target. Recently, aptamers have been identified as promising candidates for inhibiting the biological activity of biomolecules. Despite these advantages, their applications are limited due to negative charge, small size, and lower affinity compared to monoclonal antibodies. To overcome these limitations, in this study, we assessed the therapeutic effects of the gold nanoparticle (AuNPs)‐conjugated anti‐IL17 single‐stranded DNA aptamer in the imiquimod‐induced C57BL/6 psoriasis animal model. Methods Hydrogel‐containing anti‐IL17A aptamer (M2) or aptamer‐conjugated AuNPs were applied topically to the dorsal skin of the C57BL/6 mice 10 min before imiquimod treatment for 5 consecutive days. Psoriasis lesions and skin tissue sections were evaluated using the modified psoriasis area severity index (PASI) score and histology. The mRNA expression levels of inflammatory factors, including IL17A, Interleukin1β (IL1β) , and S100 calcium‐binding protein A9 ( S100A9 ), were assessed using reverse transcription‐quantitative polymerase chain reaction. Results Cumulative modified PASI score, as well as IL17A, IL1β, and S100A9 mRNA expression levels, showed a significant decrease in the mice treated with anti‐IL17A aptamer and anti‐IL17A aptamer‐conjugated AuNPs in comparison to the imiquimod group ( p < 0.05). The combination of anti‐IL17A aptamer with AuNPs in low concentrations (44 pmol) significantly reduced the thickness of the keratinocyte layer ( p < 0.05). In accordance with these results, treatment with anti‐IL17A aptamer with AuNPs improved the modified PASI score in the mice skin. Conclusion The findings of our study suggest that the anti‐inflammatory properties of anti‐IL17A (M2) aptamer are amplified when conjugated with AuNPs in the psoriasis‐like model. It seems to be a promising alternative for inhibiting the antibodies of IL17.
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