Abstract
BACKGROUND: 6-sulfoLacNAc (slan)+ monocytes, a non-classical monocyte subset, play a pro-inflammatory role in autoimmune diseases like systemic lupus erythematosus (SLE). This study evaluates the therapeutic potential of itacitinib (ITA) encapsulated in wheat germ agglutinin-functionalized nanoparticles (WGA/F127/PNPs) to target and inhibit the JAK-STAT pathway in slan+ monocytes. METHODS: We prepared ITA-loaded WGA/F127/PNPs and analyzed their binding and internalization in various leukocyte subsets using flow cytometry, focusing on slan+ and slan- monocytes. Further, peripheral blood samples from healthy controls (n = 37) and SLE patients (n = 50) were used to assess slan+ monocyte phenotypes. Co-cultures of slan+ and slan- monocytes stimulated with LPS revealed that slan+ monocytes significantly increased HLA-DR expression. RESULTS: Results showed that slan+ monocytes from SLE patients were reduced compared to healthy controls (p < 0.001) and that slan+ monocytes effectively internalized WGA/F127/PNPs, unlike slan- cells. ITA-loaded nanoparticles decreased HLA-DR, CD69, and CD86 expression, STAT1 phosphorylation, and cytokine production in IFN-γ-stimulated slan+ monocytes. Findings support WGA/F127/PNPs as a promising drug delivery system for targeting slan+ monocytes, providing new therapeutic potential for SLE. CONCLUSION: ITA-loaded WGA/F127/PNPs effectively target and suppress pro-inflammatory slan+ monocytes, presenting a promising, cell-specific therapeutic approach for managing systemic lupus erythematosus and related autoimmune disorders.