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

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.