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

ABSTRACT

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.