Construction of janus mesenchymal stem cell-hitchhiked melanin nanoparticles to modulate the Th17/Treg balance for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a common chronic inflammatory disease capable of causing the disability. Although various antioxidant strategies have been attempted for prevention and treatment of RA through scavenging the free radicals, the therapeutic effect is limited. Recently, it is reported that the unremitting course of RA intensely correlates with the persistence of immunologic memory, in which the imbalance of T helper 17 (Th17) cells/regulatory T (Treg) cells plays an important role. Herein, we constructed Janus mesenchymal stem cell (MSC)-hitchhiked melanin nanoparticles (MSCFM) for RA therapy, where one half of MSC kept intact for chemotactically migrating towards the RA inflammatory sites and efficiently restoring the Th17/Treg balance based on the property of MSCs, while the other half hitchhiked the iron-doped melanin (FM) nanoparticles (NPs) and release them to scavenge free radicals for maintaining the durability of Th17/Treg balance. In vitro studies indicated MSCFM could migrate towards CXCL12 inflammatory cytokine, scavenge reactive oxygen and nitrogen species, inhibit Th17 cell proliferation and induce Treg cell production. Further in vivo studies corroborated that intravenously injected MSCFM could target the RA site of collagen-induced arthritis mouse model and alleviate the pathological progression of RA. MSCFM holds great potential as an anti-inflammatory agent for RA management.