Multifunctional nanotherapeutics reprogramming the immunopathological landscape for rheumatoid arthritis therapy

As a prototypical and highly prevalent form of autoimmune disease, rheumatoid arthritis (RA) serves as a valuable model for elucidating pathogenic mechanisms and developing targeted and functional nanomedicines. Emerging research not only offers promising alternatives for RA patients that are incompatible with conventional disease-modifying antirheumatic drugs (DMARDs), but also inspires the engineering of innovative nanomedicines via interdisciplinary science and technology. This review presents a comprehensive overview of the immunopathological landscape of RA, emphasizing the key players in disease development and progression, including fibroblast-like synoviocyte, macrophage, lymphocyte and neutrophil, and delineates how these pathogenic processes create opportunities for targeted intervention. We highlight cutting-edge advances in microneedle-enhanced transdermal delivery, intelligent polymeric biomimetic targeting systems and multifunctional composite platforms. Furthermore, we explore critical developmental pathways for potential clinical translation by employing precision targeting strategies, advancing co-delivery technologies and integrating diagnostics with therapeutics. Collectively, these perspectives offer significant insights for refining precision treatment paradigms in RA.