Erythrocyte membrane camouflaged celastrol and bilirubin self-assembly for rheumatoid arthritis immunotherapy based on STING inhibition and RONS clearance.

Abstract

Activation of cGAS-STING signaling pathway and accumulation of reactive oxygen and nitrogen species (RONS) are important issues facing the treatment of rheumatoid arthritis (RA). Here, we report a biomimetic nano-Chinese medicine (HA-RM-Cel-BR) for RA immunotherapy based on STING inhibition of celastrol (Cel) and RONS clearance of bilirubin (BR). HA-RM-Cel-BR is constructed by the carrier-free self-assembly of active ingredients Cel and BR from traditional Chinese medicine, and then camouflaged by hyaluronic acid (HA)-modified red blood cell membranes (RM). HA-RM-Cel-BR prolongs circulation time through RM camouflage, targets inflamed joints by HA modification, and remodels the joint immune microenvironment by STING inhibition and RONS clearance. More importantly, HA-RM-Cel-BR shows excellent therapeutic effects on RA rat model, and significantly reduces hepatotoxicity associated with Cel. Our work provides a new strategy for RA immunotherapy with traditional Chinese medicine ingredients.