TABLE 3.
Targets | MoA | Therapeutics | Modality | Delivery systems | References | |
---|---|---|---|---|---|---|
Molecular level | Gene | Silenced the HMGB1 gene | HMGB1‐siRNA | siRNA | NAL nanoparticles | 73 |
Regulation of pro‐fibrotic genes in HSCs | miRNA‐29b, miRNA‐122 | miRNA | Micelle | 74 | ||
Noncoding RNAs | Knockdown of miR‐221‐3p | TuD‐miR‐221‐3p | miRNA | AAV8 | 76 | |
Dysregulated miR‐34a | Pterostilbene | Small‐molecule | N | 78 | ||
Increased circRNA SCAR expression located in the mitochondria | CircRNA SCAR expression vectors | pcD‐ciR | Mitochondria‐targeting NPs | 84 | ||
Signaling pathway | Inhibited TGF‐β1/Smad3 signaling | Umbelliferone | Small‐molecule | N | 85 | |
Inhibited hedgehog signaling | Vismodegib | Small‐molecule | cRGDyK‐liposome | 87 | ||
Inhibited TGF‐β signaling | TGF‐βR blocker | Protein | Lactococcus lactis | 88 | ||
Cellular level | Hepatocyte | Hepatocyte protection | Betulinic acid | Small‐molecule | Chitosan NPs | 93 |
Improved fibrotic primary hepatocyte functions | HNF4A mRNA | mRNA | Lipid NPs | 94 | ||
HSCs | Inhibited HSC activation | Imatinib | Small‐molecule | Liposomes | 96 | |
HSC cytotoxicity activated | GMO, miR‐29b | Small‐molecule, miRNA | PEG‐PLGA NPs | 97 | ||
Inhibited HSC proliferation and activation | Quercetin | Small‐molecule | Nanocages | 98 | ||
Transformed aHSCs to quiescent phenotype | Relaxin‐plasmid, miR‐30a‐5p mimic | Gene, miRNA | LPH NPs | 99 | ||
Destroyed the Golgi structure and downregulated collagen I production | Retinoic acid, DOX | Small‐molecule | Micelles | 100 | ||
Broke down the dense collagen stroma and inhibited aHSC | Collagenase, silibinin | Enzyme, small‐molecule | NPs | 101 | ||
Thermal ablation | Gold | Inorganic material | Nanorods | 102 | ||
Hepatic immune cells | Macrophage repolarized toward an anti‐fibrotic M1 phenotype | CSF‐1R siRNA | siRNA | Nanohydrogel | 104 | |
Modulated M2 macrophages | TSG‐6 | Cytokine | CaP@BSA NPs | 105 | ||
Tissue level | Reduced ROS levels | PD‐MC | Material | Micelle | 107 | |
Reduced MMP‐9 mRNA expression | MMP‐9 siRNA | siRNA | Vitamin A‐liposome | 108 |
Abbreviations: GMO, Germacrone; HMGB1, human high mobility group box‐1; HNF4A, hepatocyte nuclear factor 4 alpha; MMP, matrix metalloproteinase; MoA, mechanism of action.