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<p>Liver fibrosis constitutes a progressive pathological condition for which TGF-β1 pathway-targeted siRNA therapy holds considerable therapeutic potential. Nevertheless, clinical application of TGF-β1 siRNA is critically limited by inherent instability and inefficient delivery in vivo. In this study, we engineered an innovative siRNA delivery platform through the integration of turmeric-derived exosome-like nanovesicles (TDEs) with a metal-organic framework (ZIF-8) to generate TDEs@ZIF-8@TGFβ1siRNA nanoparticles, thereby enhancing siRNA delivery efficiency and therapeutic efficacy in liver fibrosis. Characterization revealed TDEs@ZIF-8@TGFβ1siRNA nanoparticles exhibited a well-defined nanostructure with a high TGF-β1 siRNA encapsulation efficiency of 64.73%. Additionally, the system exhibited pH-responsive release and lysosomal escape capabilities, significantly enhancing siRNA stability and cellular uptake efficiency. In vitro, TDEs@ZIF-8@TGFβ1siRNA effectively inhibited hepatic stellate cells (HSCs) activation, reducing TGF-β1, Collagen I, and CTGF mRNA levels by 78.6%, 72.1%, and 69.4%, respectively. In a CCl<sub>4</sub>-induced mouse model of liver fibrosis, TDEs@ZIF-8@TGFβ1siRNA treatment significantly improved hepatic function, reducing serum ALT and AST levels by 59.8% and 62.7%, respectively. Histological staining revealed a 71% reduction in fibrotic area, concomitant with marked downregulation of α-SMA and Collagen I expression by approximately 68% and 74%. Mechanistically, the therapeutic effects were mediated through TGF-β1 gene silencing and consequent inhibition of the TGF-β/Smad pathway, resulting in attenuated HSCs activation and diminished collagen deposition. These findings indicate that TDEs@ZIF-8@TGFβ1siRNA represents a promising biomimetic strategy for targeted gene therapy in liver fibrosis.</p> Graphical Abstract <p></p>

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Turmeric-derived exosome-coated ZIF-8 nanoplatform for targeted delivery of TGF-β1 siRNA in the treatment of liver fibrosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • Yanyan Jiang,
  • Xinliu Duan,
  • Zitong Qi,
  • Xuan Zhou,
  • Wenjing Song,
  • Li Jiang,
  • Yawen Yu,
  • Yueli Liu,
  • Xu Chai,
  • Xiaohu Tang,
  • Xiaoyan He,
  • Hangyu Xia,
  • Qun Liu,
  • Peng Zhang,
  • Aiping Wang

摘要

Liver fibrosis constitutes a progressive pathological condition for which TGF-β1 pathway-targeted siRNA therapy holds considerable therapeutic potential. Nevertheless, clinical application of TGF-β1 siRNA is critically limited by inherent instability and inefficient delivery in vivo. In this study, we engineered an innovative siRNA delivery platform through the integration of turmeric-derived exosome-like nanovesicles (TDEs) with a metal-organic framework (ZIF-8) to generate TDEs@ZIF-8@TGFβ1siRNA nanoparticles, thereby enhancing siRNA delivery efficiency and therapeutic efficacy in liver fibrosis. Characterization revealed TDEs@ZIF-8@TGFβ1siRNA nanoparticles exhibited a well-defined nanostructure with a high TGF-β1 siRNA encapsulation efficiency of 64.73%. Additionally, the system exhibited pH-responsive release and lysosomal escape capabilities, significantly enhancing siRNA stability and cellular uptake efficiency. In vitro, TDEs@ZIF-8@TGFβ1siRNA effectively inhibited hepatic stellate cells (HSCs) activation, reducing TGF-β1, Collagen I, and CTGF mRNA levels by 78.6%, 72.1%, and 69.4%, respectively. In a CCl4-induced mouse model of liver fibrosis, TDEs@ZIF-8@TGFβ1siRNA treatment significantly improved hepatic function, reducing serum ALT and AST levels by 59.8% and 62.7%, respectively. Histological staining revealed a 71% reduction in fibrotic area, concomitant with marked downregulation of α-SMA and Collagen I expression by approximately 68% and 74%. Mechanistically, the therapeutic effects were mediated through TGF-β1 gene silencing and consequent inhibition of the TGF-β/Smad pathway, resulting in attenuated HSCs activation and diminished collagen deposition. These findings indicate that TDEs@ZIF-8@TGFβ1siRNA represents a promising biomimetic strategy for targeted gene therapy in liver fibrosis.

Graphical Abstract