Nanomedicine-Driven Modulation of Signaling Pathways in Hepatic Fibrosis

The progression of hepatic fibrosis, a critical prelude to cirrhosis and hepatocellular carcinoma, is driven by multiple signaling pathways that activate hepatic stellate cells (HSCs) and cause excessive extracellular matrix (ECM) deposition. This review systematically examines the roles of key pathways, TGF-β1, PDGF, NF-κB, Wnt/β-catenin, and JAK/STAT, as therapeutic targets. A major focus is placed on nanotechnology-enhanced modalities, including nano-delivery systems for targeted drug, RNAi, and gene-editing tool delivery, which offer promising solutions to the low bioavailability and off-target effects of conventional agents. Although some targeted drugs have entered clinical trials, issues with delivery efficiency, treatment stability, and long-term safety persist. Meanwhile, traditional Chinese medicine (TCM) has demonstrated unique multi-target regulatory potential in modulating hepatic fibrosis signaling pathways; however, its clinical translation remains hindered by standardization issues and unclear molecular mechanisms. The integration of TCM with modern nanodelivery systems and precision medicine technologies is therefore urgently needed. We propose that the rational design of combinatorial nanomedicines, capable of multi-pathway interference and precision delivery, represents a paradigm shift from fibrosis suppression towards active fibrosis reversal, ultimately paving the way for personalized treatment of hepatic fibrosis.