Citations 1
Glomerular-Targeted Delivery of Low-Dose Prednisolone Attenuates Established Lupus Nephritis in MRL/lpr Mice
Williams, Kristof , Agyekum, Georgina , Patne, Akshata, Markoutsa, Eleni, Chellappan, David Raj, Hall, Nathan, Tian, Zhi , Soto, Nohely Hernandez, Cuadrao, Sebastian, Lozonschi, Isabella, Fu, Liying, Haight, Lilliana, Sharma, Rahul, Mohapatra, Subhra, Wang, Lei, Liu, Ruisheng, Fu, Liying, Sharma, Rahul, Wang, Lei , Mohapatra, Shyam S. , Liu, Ruisheng
No container title available | August 7, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Lupus nephritis remains a major cause of chronic kidney disease and kidney failure in systemic lupus erythematosus. Glucocorticoids are central to treatment but are limited by systemic toxicity. We evaluated whether a previously characterized collagen IV α3-targeted liposomal nanoparticle formulation carrying low-dose prednisolone could attenuate established lupus nephritis in MRL/lpr mice. Methods Female MRL/lpr mice with disease present at treatment initiation and C57BL/6J control mice received saline or collagen IV α3-targeted prednisolone-loaded nanoparticles (Col4-α3-Pred-NPs). Renal outcomes were assessed by longitudinal proteinuria, glomerular filtration rate (GFR), survival, kidney histopathology, renal IgG and C3d deposition, dUTP/TUNEL-associated injury staining, and renal cytokine/chemokine profiling. Body weight, food and water intake, and blood glucose were monitored as measures of general condition and preliminary tolerability. Results Col4-α3-Pred-NPs improved survival in MRL/lpr mice, reduced cumulative proteinuria burden, and attenuated terminal GFR decline compared with saline-treated MRL/lpr controls. Treatment reduced glomerular and tubulointerstitial injury, lowered composite EGTI histopathology scores, decreased terminal kidney enlargement, reduced glomerular IgG deposition and renal dUTP-positive injury signals, and reduced renal signals for IL-28A/B, IL-7, PD-ECGF, IL-11, CCL6/C10, and IL-15. C3d deposition was not significantly altered. Nanoparticle treatment was not associated with sustained treatment-related increases in blood glucose or body-weight loss during the measured study period. Conclusions Collagen IV α3-targeted liposomal delivery of low-dose prednisolone attenuated established lupus nephritis in MRL/lpr mice and improved renal structural, functional, inflammatory, and survival outcomes. These findings support further evaluation of glomerulus-targeted nanotherapy as a potential strategy to improve the precision and therapeutic index of glucocorticoid treatment in lupus nephritis.