Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis

Ling Guo, Shi Luo, Zhengwu Du, Meiling Zhou, Peiwen Li, Yao Fu, Xun Sun, Yuan Huang and Zhirong Zhang ()
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Ling Guo: Sichuan University
Shi Luo: Sichuan University
Zhengwu Du: Sichuan University
Meiling Zhou: Sichuan University
Peiwen Li: Sichuan University
Yao Fu: Sichuan University
Xun Sun: Sichuan University
Yuan Huang: Sichuan University
Zhirong Zhang: Sichuan University

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00834-8

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DOI: 10.1038/s41467-017-00834-8

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