Table 1 Summary of liver-targeted LNP-based mRNA delivery strategies
From: mRNA nanodelivery systems: targeting strategies and administration routes
Delivery systems | Formulation (mol%) | Administration route | Targeting features | Properties of mRNA NPs | Target cells | Ref. | ||
|---|---|---|---|---|---|---|---|---|
Size (nm) | Zeta (mV) | pKa | ||||||
Passive targeting | ||||||||
 LNP | MC3: DSPC: Chol: DMPE-PEG2000 50: 10: 38.5: 1.5 | i.v. | Size Surface composition of LNP | 65 | / | 6.44 | Hepatocytes | [46] |
 LNP | 5A2-SC8: DOPE: Chol: DMG-PEG 23.81: 23.81: 47.62: 4.76 | i.v. | Adjust the proportion of ionizable cation and zwitterionic phospholipid | 95-101 | -3.58 | 6.67 | Hepatocytes | [103] |
 LNP | 3060i10: DOPE: Chol: C14-PEG2000 35: 16: 46.5: 2.5 | i.v. | pKa | 124.6 | 0.43 | 6.40 | Hepatocytes Kupffer cells Endothelial cells | [104] |
 LNP | CLA: DOPE: Chol: DMG-PEG 31.25: 23.44: 39.06: 6.25 | i.v. | CLA | 100-150 | Neutral charge | / | / | [105] |
 LNP | 5A2-SC8: DOPE: Chol: DMG-PEG: DODAP 19: 19: 38:4: 20 | i.v. | 20% ionizable cationic lipid DODAP ApoE | 122.4 | / | 6.46 | Hepatocytes (93%) | [106] |
 LNP | cKK-E12: DOPE: 20α-OH: C14-PEG 35: 16: 46.5: 2.5 | i.v. | ApoE LDLR | 70.1 | / | / | Hepatocytes Kupffer cells DCs | [91] |
 LNP | cKK-E12/A6: DOPE: Chol: C14-PEG2000 35: 16.0: 46.5: 2.5 (A molar ratio of cKK-E12:A6 at 7:3) | i.v. | Albumin-associated macropinocytosis and endocytosis Introducing alkyne and ester groups into the lipid tails of MC3 | Fluc mRNA: 99.5 ± 0.3 hEPO mRNA: 91.2 ± 0.5 | -2.1 ± 1.3 | 6.78 ± 0.14 | Hepatocytes | [107] |
 LNP | MC3: DSPC: Chol: PEG-lipid 50: 10: 38.5: 1.5 | i.v. | ApoE | / | / | / | Hepatocytes in liver fibrosis | [14] |
 LNP | CL15A6: DOPE: cholesterol: DMG-PEG2000 50: 20: 30: 3 | i.v. | pKa Clathrin-mediated endocytosis through PDGFRβ receptors | 179.2 ± 9.04 | -9.6 ± 6.3 | 7.3 ± 0.11 | HSCs(80%) | [108] |
 LNP | MC3: DSPG: Chol: PEG-DMG 50: 10: 38.5: 1.5 | i.v. | Anionic LNP Stabilin receptors | 66.6 ± 22.0 | -20 | / | LSECs | [109] |
 LNP | cKK-E12: DOPE: 20α-OH: C18PEG2000 50: 10: 38.5: 1.5 | i.v. | Modified cholesterols | 80.1 | / | 5.6 | LSECs Kupffer cells | [110] |
Active targeting | ||||||||
 PLN | DOTAP: CHEMS: Chol: PEG2000 + GalNAPc-targeted polymer | i.v. | Active targeting (GalNAc ligand) | OTC mRNA/LNP: 65.4 ± 5.8 Polymer micelle: 15.5 ± 0.3 | LNP: 0.84 ± 0.71 Polymer: 0.78 ± 0.91 | / | Hepatocytes | [111] |
 LNP | AA-T3A-C12: DSPC: Chol: C14-PEG2000 50: 10: 38.5: 1.5 | i.v. | Active targeting (Anisamide-tethered lipidoids) | <100 | neutral charge | 5.72 | HSC Hepatocytes | [112] |
 LNP | 246C10: DOPE: Chol: C16-PEG2000 26.5: 20: 50.5: 3.0 (2.5% mannose-PEG lipid) | i.v. | Active targeting (Mannose ligand) | 117±11 | -0.997 ± 0.21 | 6.75 | LSECs | [16] |
 LNP | MC3: DSPC: Chol: DSPE-PEG2000-mannose 50: 10: 38.5: 1.5 | i.v. | Active targeting (Mannose ligand) | 153.2±1.1 | -5.37 ± 2.40 | / | LSECs | [113] |