Table 2.
Nanocarriers for cell-specific drug delivery to HSC.
| Addressed Target | Cell-Specific Ligand | In Vivo Cellular Uptake | Encapsulated Drug | In Vivo Therapeutic Effect | Nano Carrier | Size (Zeta Potential) | Reference |
|---|---|---|---|---|---|---|---|
| PDGFRβ | Cyclic peptide | HSC | IFNγ | Improved antifibrotic effect vs untargeted IFNγ | Liposomes | ~83.5 nm | [115] |
| PDGFRβ | Cyclic peptide | HSC | antiHSP 47 siRNA | Improved antifibrotic effect vs control siRNA/carriers in TAA fibrotic mice | Lipoplexes | ~110 nm (~0 mV) | [116] |
| Receptors for retinol binding protein | Vitamin A | HSC, (macrophages) | antiHSP47 siRNA | Improved antifibrotic effect vs control siRNA/carriers in liver fibrotic rats | Liposomes | ~150 nm | [117] |
| Receptors for retinol binding protein | Vitamin A | HSC | anticol1a1 and antiTIMP-1 siRNA | Antifibrotic effect vs scrambled siRNA loaded carriers in CCl4 fibrotic mice | Lipoplexes | ~140 nm (~−12.9 mV) | [118] |
| Integrin αvβ3 | Cyclic RGD peptide | Activated HSC (+++), Kupfer cells and LSECs (++), biliary cells (+), hepatocytes (+) | Vismodegib (hedgehog inhibitor) | Improved antifibrotic effect vs control drug/empty carrier in BDL fibrotic mice | Liposomes | ~80 nm, (~−24.8 mV) | [119] |
| CXCR4 | CXCR4 antagonistic peptide (CTCE9908) | HSC | Sorafenib/multi-tyrosine-kinase inhibitor | Antifibrotic and antitumor effect in mice with CCl4-induced fibrosis, HCC and PDAC | Liposomes | ~140 nm | [120] |
| No specific target | Unguided carriers | HSC (+++), Kupffer cells and LSEC (++), hepatocytes (+) | Anti-col1a1 siRNA | Antifibrotic effect vs scrambled siRNA loaded carriers in CCl4 fibrotic mice | Cationic nanohydrogel particles | ~40 nm (~0 mV) | [121,122] |
| No specific target | Unguided carriers | HSC (+++), Kupffer cells/macrophages (++), hepatocytes (+), LSEC (+) | Anti-col1a1 siRNA | Antifibrotic effect vs scramble siRNA loaded nano- carriers in CCl4 and MDR2-/- fibrotic mice | Lipid cationic nanoparticles | [123] | |
| M6P receptor | M6P | HSC > Kupffer cells > LSEC | No drug reported | No effect reported | Liposomes | ~102 nm | [124] |
CCl4, carbon tetrachloride; col1a1, collagen 1a1 gene; CXCR4, chemokine receptor type 4; ERK, extracellular signal-regulated kinases; HSC, hepatic stellate cells; HSP 47, heat shock protein 47; IFNγ, Interferon gamma; LSECs, liver sinusoidal endothelial cells; MEK, mitogen-activated protein kinase; M6P, mannose-6-phosphate; PDGFRβ, Platelet-derived growth factor receptor beta; TAA, thioacetamide; TIMP-1, TIMP tissue inhibitor of metallopeptidases 1.