IgG78‐Engineered Macrophage Membrane Biomimetic Nanoparticles for Synergistic Targeted Photothermal‐Chemotherapy of Rheumatoid Arthritis

Clinical management of rheumatoid arthritis (RA) primarily involves non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents or gene therapy; however, these treatments have notable limitations. DMARDs, particularly methotrexate (MTX), continue to be the cornerstone of first-line therapy, despite systemic side effects that restrict long-term application and heighten the treatment burden. This study identified elevated levels of CD248 in synovial fibroblasts (RA-FLS) from RA patients, which correlated with increased proliferation and migration. To improve the joint targeting of MTX, a biomimetic nanoplatform was developed using macrophage membrane coating. The anti-CD248 antibody (IgG78) was conjugated to the macrophage membrane surface and incorporated onto mesoporous polydopamine (MPDA) nanoparticles, resulting in active-targeting membrane-coated nanoparticles (MNPs). Experimental results demonstrated that MNPs exhibit exceptional specificity and affinity for RA-FLS. The MTX-loaded MPDA/MTX@M-IgG78 nanosystem showed pronounced therapeutic effects against RA. The high photothermal conversion efficiency of MPDA facilitated controlled MTX release under near-infrared laser irradiation, synergistically enhancing anti-RA efficacy. In conclusion, this innovative biomimetic approach enables targeted MTX delivery to the joints, improving therapeutic effectiveness while minimizing systemic side effects, thereby providing novel strategies for precise RA treatment.