Fe-Doped Carbon Dots Alleviated Rheumatoid Arthritis by Inhibiting Neutrophil NETosis and Autophagy

Rheumatoid arthritis (RA) is an autoimmune disorder primarily affecting joints, characterized by high incidence rates and significantly impairing patients' quality of life. Neutrophils play a pivotal role in RA pathogenesis, making therapeutic interventions targeting neutrophil-mediated inflammatory cascades a promising strategy for RA treatment. Inspired by traditional Tibetan medicinal formulations, which typically combine metallic minerals and organic components, this study developed iron-doped carbon dots (MM-CDs) via a facile one-pot synthesis approach using magnetite (Cishi) and medicated leaven (Shenqu). The therapeutic efficacy of MM-CDs was subsequently evaluated in a mouse model of RA. The results indicated that MM-CDs effectively alleviated RA by disrupting neutrophil-induced inflammatory cascades. Specifically, MM-CDs inhibited NETosis, significantly downregulated myeloperoxidase (MPO), citrullinated histone H3 (Cit-H3), and peptidyl arginine deiminase 4 (PAD-4) in joint tissues (P < 0.05). Furthermore, MM-CDs modulated autophagy pathways, suppressing LC3B and Beclin-1 expression, thereby reducing neutrophil survival. Additionally, MM-CDs promoted apoptosis in neutrophils, evidenced by increased cleaved caspase-3/PARP expression and decreased Bcl-2 levels in LPS-stimulated neutrophils. This study demonstrates that MM-CDs represent a novel and effective therapeutic strategy for RA. Importantly, the treatment exhibited no liver or kidney toxicity in the RA mouse model, highlighting its potential for safe clinical translation.