@article{Fu2026, 
author = {Jiali Fu and Yujia Wang and Anqi Zhang and Ting Li and Yan Yuan and Kejin Chen and Shanshan He and Lin Li and Shiqi Huang and Ling Guo and Xun Sun and Tao Gong and Ling Zhang and Qing Lin and Zhirong Zhang},
title = {Reticuloendothelial system blockade-assisted redirection of celastrol-loaded nanomedicine to glomeruli for treatment of mesangioproliferative glomerulonephritis},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {9},
pages = {94908676},
keywords = {celastrol, reticuloendothelial system blockade, glomerular targeting, mesangioproliferative glomerulonephritis},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908676},
doi = {10.26599/NR.2026.94908676},
abstract = {Glomerulonephritis (GN), a major cause of chronic kidney disease, remains difficult to treat due to inefficient glomerular drug delivery following systemic administration. Here, we report a targeted nanotherapeutic strategy based on celastrol (CLT)-loaded, positively charged poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CLT@R8-PLNs) designed to promote glomerular accumulation. To further improve renal targeting, a reticuloendothelial system (RES) blockade strategy was employed by pre-saturating phagocytic organs with blank nanoparticles prior to CLT@R8-PLNs administration. In vivo biodistribution studies demonstrated that RES blockade markedly reduced hepatic and splenic sequestration while significantly enhanced glomerular accumulation of the nanoparticles. In a rat model of mesangioproliferative glomerulonephritis (MsPGN), this delivery strategy effectively alleviated glomerular inflammation and suppressed mesangial cell proliferation, accompanied by pronounced downregulation of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, interleukin-6, interleukin-1β, and proliferating cell nuclear antigen. Collectively, these results demonstrate that integrating RES blockade with size-dependent passive targeting and charge-mediated glomerular interactions enables enhanced glomerular delivery and therapeutic efficacy, providing a rational nanomedicine-based approach for the treatment of GN.}
}