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Senescence of Hepatic Stellate Cells by Specific Delivery of Manganese for Limiting Liver Fibrosis.
Gu, Lihong; Zhao, Chenxuan; Wang, Yixuan; Wang, Chao; Yin, Xiaochun; Ye, Qingsong; Liu, Yan; Zou, Xiaoping; Wang, Lei; Zhuge, Yuzheng; Wu, Jinhui; Zhang, Feng.
Affiliation
  • Gu L; Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, People's Republic of China.
  • Zhao C; State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Wang Y; Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Wang C; Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, People's Republic of China.
  • Yin X; State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Ye Q; Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Liu Y; State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Zou X; Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Wang L; State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Zhuge Y; Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
  • Wu J; Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, People's Republic of China.
  • Zhang F; State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, Jiangsu 210093, People's Republic of China.
Nano Lett ; 24(4): 1062-1073, 2024 Jan 31.
Article in En | MEDLINE | ID: mdl-38164915
ABSTRACT
Senescence of activated hepatic stellate cells (HSCs) is crucial for the regression of liver fibrosis. However, impaired immune clearance can result in the accumulation of senescent HSCs, exacerbating liver fibrosis. The activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is essential for both senescence and the innate immune response. Additionally, the specific delivery to activated HSCs is hindered by their inaccessible anatomical location, capillarization of liver sinusoidal endothelial cells (LSECs), and loss of substance exchange. Herein, we propose an antifibrotic strategy that combines prosenescence with enhanced immune clearance through targeted delivery of manganese (a cGAS-STING stimulator) via albumin-mediated transcytosis, specifically aimed at inducing senescence and eliminating activated HSCs in liver fibrosis. Our findings demonstrate that only albumin efficiently transfers manganese to activated HSCs from LSECs via transcytosis compared to liposomes, resulting in significant antifibrotic effects in vivo while exhibiting negligible toxicity.
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Full text: 1 Database: MEDLINE Main subject: Hepatic Stellate Cells / Liver Limits: Humans Language: En Journal: Nano Lett Year: 2024 Type: Article

Full text: 1 Database: MEDLINE Main subject: Hepatic Stellate Cells / Liver Limits: Humans Language: En Journal: Nano Lett Year: 2024 Type: Article