Delivery of Dexamethasone Using Folate-Targeted Au Nanoflowers for Rheumatoid Arthritis Therapy

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disorder characterized by joint pain and progressive damage that can severely impair daily activities and reduce overall quality of life. The long-term, high-dose administration of conventional drugs often results in severe adverse effects. In this study, we designed a multifunctional nanoplatform for synergetic chemo-photothermal therapy (chemo-PTT) of RA. Au nanoflowers (AuNFs) were prepared using the l-ascorbic acid reduction method, and the surface of AuNFs was modified with FA-SH and SH-β-CD through gold-sulfur bonds. Consequently, dexamethasone (DEX)-loaded FA-AuNFs-CD was constructed (designed as FA-AuNFs-CD/DEX). Lipopolysaccharide (LPS) was used to stimulate an inflammatory response, and DEX-loaded AuNFs were evaluated for their anti-inflammatory effects using a RAW264.7 cell inflammatory model. An adjuvant arthritis rat model was established to observe the anti-RA effect of FA-AuNFs-CD/DEX under 808 nm near-infrared (NIR) laser irradiation. <i>In vivo</i> and <i>in vitro</i> evaluations revealed that the combined chemo-PTT effectively eliminated enriched inflammatory cells in the joint cavity and significantly reduced the production of many inflammatory cytokines, demonstrating promising anti-RA effects in the adjuvant-induced arthritis (AIA) rat model. In conclusion, the combination of chemo-PTT offers a potential new therapeutic strategy for RA treatment.