Orally delivered 2D covalent organic frameworks releasing kynurenine generate anti-inflammatory T cell responses in collagen induced arthritis mouse model

Abstract

Covalent organic framework (COF) crystalline biomaterials have great potential for drug delivery since they can load large amounts of small molecules (e.g. metabolites) and release them in a controlled manner, as compared to their amorphous counterparts. Herein, we screened different metabolites for their ability to modulate T cell responses in vitro and identified Kynurenine (KyH) as a key metabolite that not only decreases frequency of pro-inflammatory RORgt + T cells but also supports frequency of anti-inflammatory GATA3+ T cells. Moreover, we developed a methodology to generate imine-based TAPB-PDA COF at room temperature and loaded these COFs with KyH. KyH loaded COFs (COF-KyH) were able to then release KyH in a controlled manner for 5 days in vitro. Notably, COF-KyH when delivered orally in mice induced with collagen-induced rheumatoid arthritis (CIA) were able to increase frequency of anti-inflammatory GATA3+CD8⁺ T cells in the lymph nodes and decrease antibody titers in the serum as compared to the controls. Overall, these data demonstrate that COFs can be an excellent drug delivery vehicle for delivering immune modulating small molecule metabolites.

Keywords: Covalent organic framework; Drug delivery; Kynurenine; Metabolites; Rheumatoid arthritis.