Sublingual dendritic cells targeting by aptamer: Possible approach for improvement of sublingual immunotherapy efficacy

• Published in: International immunopharmacology 2020-08, Vol.85, p.106603, Article 106603
• Main Authors: Keshavarz Shahbaz, Sanaz, Varasteh, Abdol-Reza, Koushki, Khadijeh, Ayati, Seyed Hasan, Mashayekhi, Kazem, Sadeghi, Mahvash, Moghadam, Malihe, Sankian, Mojtaba
• Format: Article
• Language: English
• Subjects: Allergens; Allergens - administration & dosage; Allergic diseases; Allergies; Animals; Antibodies; Aptamer; Aptamers; Aptamers, Nucleotide - administration & dosage; Cell growth; Cell proliferation; Counting; Dendritic cells; Dendritic Cells - immunology; Enzyme-linked immunosorbent assay; Evaporation; Female; Hypersensitivity; Immunoglobulin E; Immunotherapy; Interleukin 1; Interleukin 10; Interleukin 17; Interleukin 4; Lymphocytes; Lymphocytes T; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - administration & dosage; Oral administration; Ovalbumin; Ovalbumin - administration & dosage; PLGA NPs; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage; Polylactide-co-glycolide; Respiratory tract diseases; Rhinitis allergic diseases; Rhinitis, Allergic - therapy; SLIT; Sublingual Immunotherapy; γ-Interferon
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106603

[Display omitted] •The reduction of required allergens with maximum efficiency is the main purpose of the SLIT.•Allergen encapsulation in PLGA NPs decreases the undesired allergic side effects.•Sublingual DC cells play a central role in SLIT.•The specific targeting of allergen to Sublingual DC cells significantly improved the efficacy of SLIT.•DC-specific aptamers could be applied for specific targeting of allergen-encapsulated NPs to sublingual DC cells. The efficacy improvement of current sublingual immunotherapy (SLIT) for preventing and treating respiratory airway allergic diseases is the main purpose of many investigations. In this study, we aimed to assess whether ovalbumin (Ova) encapsulated poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) decorated with dendritic cells (DCs)-specific aptamer could be applied for this purpose.The nanoparticles containing Ova were synthesized by emulsion/solvent evaporation method and attached to DCs-specific aptamer. Ova-sensitized BALB/c mice have been treated in five ways: subcutaneously with free Ova (SCIT), sublingually either with free Ova, Ova-PLGA NPs (two doses), Apt-Ova-PLGA NPs (two doses) and placebo/control Apt-Ova-PLGA NPs. For assessment of immunologic responses, IL-4, IFN-γ, IL-17, IL10, and TGF-β and IgE antibody levels were measured by ELISA and T cell proliferation were evaluated by MTT. In addition, lung and nasal histological examinations, NALF cells counting were carried out. Results declared that the lowest IgE and IL- 4 levels were observed in Apt-Ova-PLGA NPs (both doses). In the other hands, Apt-Ova-PLGA NPs (high dose) showed the highest increase of IFN- γ and TGF- β, decrease of IL-17 levels, total cell count and T-cell proliferation. IL-10 levels showed more decrease in SCIT, Apt-Ova-PLGA NPs (high dose) and Ova-PLGA NPs (high dose) than other groups. Histopathological examinations also confirmed in vitro results. Our findings suggest SLIT with this functionalized delivery system could be a promising approach for promoting the SLIT efficiency by decreasing the required allergen doses through specific delivery of allergen to sublingual DCs and enhancing the suppression of allergic responses.