2022年1月
Nitric oxide facilitates the targeting Kupffer cells of a nano-antioxidant for the treatment of NASH.
Journal of controlled release : official journal of the Controlled Release Society
- 巻
- 341
- 号
- 開始ページ
- 457
- 終了ページ
- 474
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jconrel.2021.11.039
Kupffer cells are a key source of reactive oxygen species (ROS) and are implicated in the development of steatohepatitis and fibrosis in nonalcoholic steatohepatitis (NASH). We recently developed a polythiolated and mannosylated human serum albumin (SH-Man-HSA), a nano-antioxidant that targets Kupffer cells, in which the mannosyl units on albumin allows their specific uptake by Kupffer cells via the mannose receptor C type 1 (MRC1), and in which the polythiolation confers antioxidant activity. The aim of this study was to investigate the therapeutic potential of SH-Man-HSA in NASH model mice. In livers from mice and/or patients with NASH, we observed a reduced blood flow in the liver lobes and the down-regulation in MRC1 expression in Kupffer cells, and SH-Man-HSA alone failed to improve the pathological phenotype in NASH. However, the administration of a nitric oxide (NO) donor restored hepatic blood flow and increased the expression of the mannose receptor C type 2 (MRC2) instead of MRC1. Consequently, treatment with a combination of SH-Man-HSA and an NO donor improved oxidative stress-associated pathology. Finally, we developed a hybrid type of nano-antioxidant (SNO-Man-HSA) via the S-nitrosation of SH-Man-HSA. This nanomedicine efficiently delivered both NO and thiol groups to the liver, with a hepatoprotective effect that was comparable to the combination therapy of SH-Man-HSA and an NO donor. These findings suggest that SNO-Man-HSA has the potential for functioning as a novel nano-therapy for the treatment of NASH.
- リンク情報
- ID情報
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- DOI : 10.1016/j.jconrel.2021.11.039
- PubMed ID : 34856227