TRAIL-expressing cell membrane nanovesicles as an anti-inflammatory platform for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Although the progress made with current clinical use of biologic disease-modifying antirheumatic drugs (bioDMARDs), the response rate of RA treatment remains ungratified, primarily due to intricacy interactions of multiple inflammatory cytokines and the awkward drug delivery. Thus, it is of great importance to neutralize cytokines and actively deliver therapeutic agents to RA joints for the purpose of promoting in situ activity. Herein, we proposed and validated a nanoparticle-based broad-spectrum anti-inflammatory strategy for RA management by fusing TRAIL-anchored cell membranes onto drug-loaded polymeric cores (TU-NPs), which makes them ideal decoys of inflamed macrophage-targeted biological molecules. Upon intravenous injection of TU-NPs into collagen-induced arthritic mice, the fluorescence/photoacoustic dual-modal imaging revealed higher accumulations and longer retention of TU-NPs in inflamed joints. In vivo therapeutic evaluations suggested that these nanoparticles could neutralize cytokines, suppress synovial inflammation, and provide strong chondroprotection against joint damage by targeting and deep penetration into the inflamed tissues. Overall, our work provides a novel strategy to treat RA with a strong potential for clinical translation. TRAIL-UVECs derived cell membrane was extracted and coated onto the HCQ-PLGA nanoparticles (TU-NPs), which inherit the source cell membrane receptors and TRAIL RA targeting ability. Due to the existence of TRAIL and inflammatory cytokines receptors, TU-NPs can actively target the inflamed joints and active macrophages to delivery antirheumatic drugs and neutralize the secreted cytokines, thus protect the cartilage and bone from erosion and destruction, and alleviate the progression of RA. Unlabelled Image [ABSTRACT FROM AUTHOR]