Abstract: SA-PO724
Targeting M2b Macrophages by Selenium Nanomedicine for the Treatment of Lupus Nephritis
Session Information
- Glomerular Diseases: Therapeutic Strategies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Zhou, Yiming, Sun Yan-sen Memorial Hospital,Sun Yan-sen University, Guangzhou, China
- Lv, Haoran, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Liang, Hanzhi, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Wang, Le, Sun Yan-sen Memorial Hospital,Sun Yan-sen University, Guangzhou, China
- Luo, Siweier, Sun Yan-sen Memorial Hospital,Sun Yan-sen University, Guangzhou, China
- Liu, Qinghua, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Background
Excessive activation of macrophages, particularly M2b macrophages, plays a pivotal role in the progression of lupus nephritis (LN); however, effective treatment strategies remain limited. Selenium possesses immunomodulatory properties; nevertheless, its high toxicity and instability hinder its application. Here, we designed and constructed novel selenium nanoparticles for the treatment of LN by targeting M2b macrophages.
Methods
Primary mouse macrophages were used to observe the toxicity and targeting ability of selenium nanomedicine on macrophages, as well as the immune-regulation of macrophage activation by LPS. RNA-seq and qPCR experiments were used to explore the molecular mechanism of selenium nanoparticles on macrophage activation. Finally, a lupus mouse model was used to investigate the renal protective effect of selenium nanoparticles in vivo.
Results
Selenium nanoparticles exhibited excellent stability and biocompatibility. By coating mannose to the selenium nanoparticles, they could selectively target M2b macrophages both in vitro and in vivo, and display increased retention time in kidneys of lupus mice. Selenium nanoparticles significantly inhibited macrophage activation and reduced the expression and releasing of pro-inflammatory cytokines and chemokines. In addition, selenium nanoparticles significantly attunated the ROS production and improved the mitochondrial function in M2b macrophages. Mechanistically, we discovered that selenium nanoparticles regulate M2b macrophages via the JAK1/JAK2-STAT1 pathway through GPX1 expression. In animal, these nanoparticles significantly improved the renal function, preserved the renal structure, and reduced the renal fibrosis by inhibiting M2b macrophage activation in mice with lupus nephritis.
Conclusion
In this study, we developed a novel selenium nanomedicine that selectively targets M2b macrophages and suppresses their activation by attenuating the ROS production and inhibiting the JAK1/JAK2/STAT1 pathway through GPX1 expression, thereby achieving therapeutic efficacy in LN. Our findings provide a new idea for the treatment of LN by targeting specific macrophage population.