Tannic Acid-Based Nanomaterials for Tolerogenic Immunotherapy of Rheumatoid Arthritis

Here, a tannic acid-based nanomaterial is developed for treating rheumatoid arthritis by inducing antigen-specific immune tolerance. The tolerogenic nanovaccine is designed for targeted delivery of dexamethasone and citrullinated peptide in a lipid-coated nanoparticle consisting of tannic acid as core nanomaterial (CitDTN). The surface of CitDTN is modified with abatacept to yield AbaCitDTN. Abatacept modification enables the tolerogenic nanovaccine to target dendritic cells by interacting with the co-stimulatory molecules, CD80 and CD86. This modification increases the lymph node accumulation of the tolerogenic nanovaccine upon subcutaneous administration. In addition, AbaCitDTN reprograms the properties of dendritic cells toward tolerogenic phenotypes and interrupts co-stimulatory signals between dendritic cells and T cells, leading to suppressed T cell proliferation and interlukin-2 secretion. Collagen-induced arthritis DBA/1 model mice are subcutaneously administered with AbaCitDTN weekly for a total of four injections. This reduces inflammation in the synovial space and decreases autoimmunity against type II collagen and citrullinated peptide. In vivo administration of AbaCitDTN improves clinical symptoms and protects joints from destruction in this animal model. These findings suggest that tannic acid-based nanomaterials could have potential to induce antigen-specific immune tolerance for treating rheumatoid arthritis.