Polypropylene sulfide methotrexate nanoparticles target the synovial lymphatic system to restore immune tolerance in rheumatoid arthritis

Around 40 % of patients fail to achieve primary clinical outcomes for rheumatoid arthritis (RA). The growth of lymphatic system in the synovial membrane, is a primary response during RA inflammation. It is suggested that a delivery strategy targeting immunosuppressive agents to the synovial lymph nodes and then to the immune cells is beneficial for resolving arthritis. This study introduced a synthetic polypropylene sulfide methotrexate nano-delivery system (PPS-MTX), which was prepared by covalently bonding methotrexate to polypropylene sulfide, with a diameter size range of 36 nm. It enhanced joint accumulation and retention, which can be selectively uptake by antigen-presenting cells in the synovial lymphatic system. The results indicated that PPS-MTX nanoparticles effectively improved arthritis disease progression and restored the immune tolerance microenvironment in the synovial lymphatic system, promoting peripheral tolerance in collagen-induced arthritis mice. Additionally, no systemic toxicity was observed. This study presents a promising targeted strategy for inducing immune tolerance in the treatment of rheumatoid arthritis.