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

Abstract

Background: 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.

Methods: 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.

Conclusion: 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.