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. The abnormal immunopathological landscape of rheumatoid arthritis (RA) has become a critical therapeutic target, especially for innovative nanomedicine. This review presents a comprehensive overview of the immunopathological landscape of RA, and delineates how these pathogenic processes create opportunities for targeted intervention via nanomedicines. The current challenges and further perspectives of effective RA therapy are further discussed.