Alvarez Karen, Anacona Cristian A, Agudelo Esneyder Ruiz, Losada Paula, Orozco Víctor H, Giraldo Luis Fernando, Vásquez Gloria, Rodriguez Daniel, Díaz Juan Camilo, Pineda Ricardo, Rojas Mauricio
Cellular Immunology and Immunogenetics Group (GICIG), Faculty of Medicine, University of Antioquia, Medellin, Colombia.
Polymer Research Laboratory, University of Antioquia, Medellin, Colombia.
Nanomedicine (Lond). 2025 May;20(10):1113-1126. doi: 10.1080/17435889.2025.2494500. Epub 2025 Apr 28.
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.
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 ( = 37) and SLE patients ( = 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 showed that slan+ monocytes from SLE patients were reduced compared to healthy controls ( < 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.
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.
6-磺基乳糖胺（slan）+单核细胞是一种非经典单核细胞亚群，在系统性红斑狼疮（SLE）等自身免疫性疾病中发挥促炎作用。本研究评估了包裹在麦胚凝集素功能化纳米颗粒（WGA/F127/PNPs）中的itacitinib（ITA）靶向并抑制slan+单核细胞中JAK-STAT通路的治疗潜力。
我们制备了负载ITA的WGA/F127/PNPs，并使用流式细胞术分析了它们在各种白细胞亚群中的结合和内化情况，重点关注slan+和slan-单核细胞。此外，还使用了来自健康对照者（n = 37）和SLE患者（n = 50）的外周血样本评估slan+单核细胞表型。用脂多糖刺激slan+和slan-单核细胞的共培养显示，slan+单核细胞显著增加了HLA-DR表达。
结果显示，与健康对照者相比，SLE患者的slan+单核细胞减少（P < 0.001），且与slan-细胞不同，slan+单核细胞能有效内化WGA/F127/PNPs。负载ITA的纳米颗粒降低了IFN-γ刺激的slan+单核细胞中HLA-DR、CD69和CD86的表达、STAT1磷酸化以及细胞因子的产生。研究结果支持WGA/F127/PNPs作为一种有前景的靶向slan+单核细胞的药物递送系统，为SLE提供了新的治疗潜力。
负载ITA的WGA/F127/PNPs能有效靶向并抑制促炎性slan+单核细胞，为治疗系统性红斑狼疮及相关自身免疫性疾病提供了一种有前景的、细胞特异性的治疗方法。
