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

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.

Automated summary

Covalent organic frameworks (COFs) are potential drug delivery biomaterials that can load and control release small molecules in a crystalline form. In this study, Kyurenine (KyH) was identified as a key metabolite that modulates T cell responses, increasing anti-inflammatory and reducing pro-inflammatory T cell frequencies. The researchers developed a method to generate imine-based COFs and loaded them with KyH, enabling controlled release for 5 days. When orally delivered to mice with rheumatoid arthritis, the KyH-loaded COFs increased anti-inflammatory T cell frequencies and decreased antibody titers. These findings demonstrate the potential of COFs as drug delivery vehicles for immune modulation.