Decoy Interleukin-1 Receptor Antagonist on Extracellular Vesicles

Abstract

Interleukin-1 (IL-1) is an important inflammatory factor in multi-organ inflammation and tissue damage. Interleukin-1 receptor antagonist (IL-1RA) is a bioactive receptor for IL-1. The interaction of these two—IL-1 and its particular receptor antagonist, IL-1RA—influences the propensity and severity of numerous illnesses. Importantly, therapies using IL-1RA have been applied in treatment of human inflammatory diseases like rheumatoid arthritis. In this study, we designed a “decoy” cell-derived nanocapsule, which uses stably-expressed HEK293T cells to display the IL-1RA on the outer surface of exosomes to act as a decoy antagonist against IL-1. After preparation, the decoy exosomes were characterized using Western Blot, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA) to confirm whether they retained the correct size and shape of naturally-occurring exosomes. Results indicated that the IL-1Ra protein was successfully expressed on exosomes that had been secreted by HEK293T cells that were transfected with a pcDNA3.1(+)-IL-1RA-N-termSyntenin recombinant plasmid. This work provides a favorable, exosome-based tool for the targeted delivery of IL-1Ra for the treatment of joint inflammatory diseases.