Receptor-Guided Nanomedicine for Rheumatoid Arthritis: Linking Target Biology, Nanocarrier Design, and Translation.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis and progressive joint destruction. Although current therapies improve disease control, inadequate lesion selectivity, heterogeneous responses, and systemic toxicity remain important limitations. Receptor-guided nanomedicine offers a strategy to align drug delivery with disease-relevant cell populations and pathological processes. This Review examines how receptor biology and pharmacological characteristics shape ligand selection, carrier architecture, payload choice, administration route, and microenvironment-responsive design in RA nanotherapy. Particular emphasis is placed on folate receptor-β (FRβ) and CD44, which represent the most extensively investigated receptor axes for activated macrophages and broader synovial cell populations, respectively. Representative platforms delivering antirheumatic drugs, glucocorticoids, natural products, nucleic acids, and functional nanomaterials are comparatively analyzed, while emerging targets including scavenger receptors, Fc gamma receptor I, pattern-recognition receptors, and integrin αvβ3 are discussed in their pathological contexts. Key translational issues, including receptor heterogeneity, target validation, formulation complexity, long-term safety, manufacturability, and patient stratification, are highlighted. Linking target biology with nanocarrier design may support more rational development of receptor-guided nanomedicines for RA.