Passively Targeted Polymeric Nanocarrier Delivering STAT1 siRNA to the Liver Ameliorates Steatohepatitis and Fibrosis in the Thioacetamide Mouse Model.
Liver fibrosis is a major complication of chronic liver injury, driven in part by Signal Transducer and Activator of Transcription 1 (Stat1). This study evaluated passively liver-targeted polymeric nanocarriers delivering Stat1 siRNA (siSTAT1) to treat steatohepatitis and fibrosis in a thioacetamide (TAA) mouse model. Two polyplex nanocarriers with different core-corona ratios, EN15 and EN76, were tested in TAA-treated mice and activated human and murine hepatocytes. In vitro, both formulations enabled efficient cellular uptake and Stat1 silencing, reducing TAA-induced lipid accumulation. Through an In vivo approach, mice received TAA for 16 weeks followed by four weeks of siSTAT1 treatment. Both formulations reduced collagen deposition, hepatic inflammation, and fibrosis scores. Notably, EN76, which preferentially targets non-parenchymal cells, showed superior antifibrotic efficacy compared with EN15. These findings highlight Stat1 as a key driver of steatohepatitis and fibrosis and support passive siRNA delivery, particularly via EN76, as a promising therapeutic strategy.
Liver fibrosis lacks effective therapies largely due to the inability of conventional lipid nanoparticles (LNPs) to target activated hepatic stellate cells (HSCs), the primary drivers of fibrotic progression. Here, we developed a fibroblast activation protein inhibitor (FAPi)-modified LNP encapsulating heat shock prote...
Ru-Lan Feng, Shu-Lei Zhu, Zi-Jun Yao et al.· Small· 0 citations
Liver fibrosis and its terminal stage, cirrhosis, represent a major cause of morbidity and mortality related to hepatic pathologies. Activated hepatic stellate cells (aHSCs) are the principal drivers of fibrogenesis and therefore constitute key therapeutic targets. Lanifibranor, a pan‐peroxisome proliferator‐activated...
Yi-Nuo Yang, Meng-Yao Mu, Ke Ren et al.· Advanced Healthcare Material...· 0 citations
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Zhao-Qi Lv, Ke Wang, Xin Di et al.· International Journal of Nan...· 0 citations
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Despite metabolic dysfunction–associated steatohepatitis (MASH) being a significant global health concern, there are few effective ways to prevent or treat MASH. Evidence from preclinical and clinical studies suggests that inflammatory polarization of Kupffer cells (KCs) and infiltration of monocyte-derived macrophages...
Kai-Ge Chen, Lu-Lu Wang, Liang Liu et al.· Bioactive Materials· 0 citations
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible lung disease with limited treatment options. SGC-CBP30, a CBP/EP300 inhibitor, shows anti-fibrotic activity but suffers from poor bioavailability and tissue specificity. Here, we developed platelet membrane-coated nanoparticles (PNP) for targeted pulm...
Yong-Hang Fan, Jian-Fen Su, Zhi-Da Chen et al.· Molecular Pharmaceutics· 0 citations
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