Reticuloendothelial system blockade-assisted redirection of celastrol-loaded nanomedicine to glomeruli for treatment of mesangioproliferative glomerulonephritis
Year: 2026
Type: article
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.
Source: Nano Research
Authors: Jiali Fu, Yujia Wang, Anqi Zhang, Ting Li, Yan Yuan, Kejin Chen, Shanshan He, Lin Li, Shiqi Huang, Ling Guo, Xun Sun, Tao Gong, Ling Zhang, Qing Lin, Zhirong Zhang
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,290
OpenAlex ID: W7148763104