CXCR4‐Expressing Mesenchymal Stem Cells Derived Nanovesicles for Rheumatoid Arthritis Treatment

Cell membrane camouflage technology, which a demonstrated value for the bionic replication of natural cell membrane properties, is an active area of ongoing research readily applicable to nanomedicine. How to realize immune evasion, slow down the clearance from the body, and improve targeting are still worth great efforts for this technology. Herein, novel cell membrane-mimicked nanovesicles from genetically engineered mesenchymal stem cells (MSCs) are presented as a potential anti-inflammatory platform for rheumatoid arthritis (RA) management. Utilizing the synthetic biology approach, the biomimetic nanoparticles are constructed by fusing C-X-C motif chemokine receptor4 (CXCR4)-anchored MSC membranes onto drug-loaded polymeric cores (MCPNs), which make them ideal decoys of stromal cell-derived factor-1 (SDF-1)-targeted arthritis. These resulting nanocomplexes function to escape from the immune system and enhance accumulation in the established inflamed joints via the CXCR4/SDF-1 chemotactic signal axis, thereby achieving an affinity to activated macrophages and synovial fibroblasts. It is further demonstrated that the MCPNs can significantly suppress synovial inflammation and relieve pathological conditions with favorable safety properties in collagen-induced arthritis mice. These findings indicate the clinical value of MCPNs as biomimetic nanodrugs for RA therapy and related diseases.