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. 2025 May;20(10):1113-1126.
doi: 10.1080/17435889.2025.2494500. Epub 2025 Apr 28.

Wheat germ agglutinin-nanoparticles encapsulating itacitinib target and suppress pro-inflammatory slan+ monocytes

Karen Alvarez  1 , Cristian A Anacona  1 , Esneyder Ruiz Agudelo  2 , Paula Losada  1 , Víctor H Orozco  2 , Luis Fernando Giraldo  2 , Gloria Vásquez  1   3 , Daniel Rodriguez  4 , Juan Camilo Díaz  4 , Ricardo Pineda  4 , Mauricio Rojas  1   5
Affiliations

Wheat germ agglutinin-nanoparticles encapsulating itacitinib target and suppress pro-inflammatory slan+ monocytes

Karen Alvarez et al. Nanomedicine (Lond). 2025 May.

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.

Keywords: PLGA nanoparticles; Slan monocytes; janus kinase inhibitors; lupus; wheat germ agglutinin.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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