DC-targeted gold nanoparticles as an efficient and biocompatible carrier for modulating allergic responses in sublingual immunotherapy

Abstract

Background: Sublingual immunotherapy (SLIT) was introduced to deliver allergens in an effective and non-invasive route, which can be considered as an alternative for allergen-specific subcutaneous immunotherapy (SCIT). On the other hand, the use of gold nanoparticles (AuNPs) in allergen delivery has beneficial effects on sublingual immunotherapy. In addition, the molecular targeting agents like aptamers (Apt), have been widely applied for targeted drug delivery. Therefore, the current study aimed to evaluate the effects of dendritic cells (DCs)-specific Aptamer-modified AuNPs coated with ovalbumin (OVA) on the improvement of the SLIT outcome in the mouse model of allergy.

Material and methods: AuNPs with approximately 15 nm diameter were prepared by citrate reduction of HAuCl4. Afterward, Apt-modified AuNP complex was prepared and OVA was then loaded onto this complex. Following sensitization of Balb/c mice to OVA, SLIT was performed with Apt-AuNPs containing 5 µg OVA twice a week for a 2-month period. Allergen-specific IgE in serum, as well as cytokines secretion of spleen cells, were analyzed using ELISA. Also, nasopharyngeal lavage Fluid (NALF) was collected for total and eosinophil counts. Moreover, the lungs were removed for histopathological examination.

Results: SLIT with Apt-modified AuNPs complex containing 5 μg OVA, decreased the IgE levels compared to the other groups. Also, IL-4 production has significantly decreased in spleen cells, while TGF-β and IFN-γ have significantly increased. The assessment of NALF in the group treated by this complex showed a decrease in total cell as well as in eosinophil count. Also, the examination of lung tissues revealed that, in the group treated by this complex, inflammation and perivascular infiltration were lesser than the other groups, which were observed in only one vessel of tissue.

Conclusion: It was shown that, Sublingual immunotherapy with DC specific Apt-modified AuNPs containing 5 μg OVA can improve the Th1 and Treg immunomodulatory responses.

Keywords: DC-specific aptamer; Gold nanoparticles (AuNPs); IgE; Ovalbumin (OVA); Sublingual immunotherapy (SLIT).