2. Academic Validation
  3. Rubicon siRNA-encapsulated liver-targeting nanoliposome is a promising therapeutic for non-alcoholic fatty liver disease

Rubicon siRNA-encapsulated liver-targeting nanoliposome is a promising therapeutic for non-alcoholic fatty liver disease

  • Int J Pharm. 2025 Jan 27:672:125291. doi: 10.1016/j.ijpharm.2025.125291.
Yuting Zhang 1,  Hanqi Wang 2,  Caili Xu 3,  Xiaomiao Ye 4,  Yanyang Nan 5,  Xiaozhi Hu 6,  Jiajun Fan 7,  Xuebin Wang 8,  Dianwen Ju 9
Affiliations

Affiliations

  • 1 Minhang Hospital Fudan University Shanghai China; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: 19261030007@fudan.edu.cn.
  • 2 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: wanghanqi@fudan.edu.cn.
  • 3 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: 21111030069@m.fudan.edu.cn.
  • 4 Minhang Hospital Fudan University Shanghai China. Electronic address: 18211360002@fudan.edu.cn.
  • 5 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: 20111030070@fudan.edu.cn.
  • 6 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: 19111030057@fudan.edu.cn.
  • 7 Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China; Shanghai Hailu Biological Technology Co., Ltd, Shanghai 201200 China. Electronic address: jiajunfan12@fudan.edu.cn.
  • 8 Department of Pharmacy, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: binxuewang@sjtu.edu.cn.
  • 9 Minhang Hospital Fudan University Shanghai China; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy Shanghai China. Electronic address: dianwenju@fudan.edu.cn.
PMID: 39880145 DOI: 10.1016/j.ijpharm.2025.125291
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic liver disorder worldwide, and effective therapeutic strategies for its treatment remains limited. In this article, we introduced Glipo-siRubi, a hepatocytes-targeting RNA interference (RNAi) nanoliposome for suppression of Rubicon expression, aiming to achieve precise regulation of Autophagy in NAFLD. Autophagy activation induced by Rubicon suppression resulted in reduced endoplasmic reticulum stress and intracellular lipid accumulation in vitro. Moreover, Glipo-siRubi administration exhibited remarkable therapeutic efficacy, characterized by decreased liver lipid accumulation, ameliorated histopathology and improved Insulin sensitivity in mice with western diet, indicating its notable potential against NAFLD. By inducing Autophagy activation, the hepatocytes-targeting Glipo-siRubi provided a promising method for NAFLD treatment, addressing the limitations of current approaches. Our study highlighted the significance of Rubicon-specific suppression in NAFLD treatment, offering a specific, safe, and efficient approach to mitigate NAFLD.

Keywords

Autophagy; Nanoliposome; Non-alcoholic fatty liver disease; Rubicon; siRNA.

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