Table 2 Summary of lung-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 | 5A2-SC8: DOPE: Chol: DMG-PEG: DOTAP 11.9: 11.9: 23.8: 2.4: 50 | i.v.ss | 50% permanently cationic lipids DOTAP pKa Vitronectin | 113.1 | -0.52 | >11.0 | Endothelial cells (<65%) Epithelial cells (<40%) Immune cells (<21%) | [106] |
 LNP | 306O10: DOTAP: Chol: C14-PEG2000 35: 40: 22.58: 2.5 | i.v. | 40% DOTAPs | ~100 | -3.5 | / | Cells in blood vessels | [141] |
 LNP | cKK-E12: 18:0 DDAB: Chol: C14-PEG2000 35: 44.5: 18: 2.5 | i.v. | Cationic helper lipid 18:0 DDAB | 106 | 1.81 | 7.7 | Lung endothelial cells | [142] |
 LNP | 306-N16B: DOPC: Chol: DMG-PEG2000 50: 10: 38.5: 1.5 | i.v. | An amide bond in the tail | 81 | -5.0 | / | Endothelial cells (69.6%) Macrophages (18.9%) Epithelium cells (7.3%) | [143] |
 LNP | 7C1: DOTAP: Chol: C14-PEG2000 35: 5: 5: 55 | i.n. | Cationic helper lipids DOTAP High molar ratio of PEG | 65.5 | / | / | Epithelial cell | [13] |
 LNP | DOTAP: MC3: DPPC: Chol: DSPE-PEG 40: 25: 10: 23.5: 1.5 | i.n. | DSPE-PEG | 38.8 ± 1.3 | 7.4 ± 1.4 | / | Alveolar epithelial type 2 cells Fibroblasts | [144] |
 LNP | MC3: DSPC: Chol: DMG-PEG2000 50: 10: 38.5: 1.5 | i.n. | PEG shells | 104.2 ± 30.5 | / | / | Airway epithelial cells in cystic fibrosis | [145] |
 LNP | ionizable lipids: helper lipids: Chol: DMG-PEG2000 50: 10: 38.5: 1.5 | i.n. | Helper lipids DOPC or ESM | 68.95 (DOPC) 72.31 (ESM) | Neutral charge | / | Epithelium cells | [146] |
 PLN | PEG-grafted PEI (PEG: 0.5%) | i.v. | PEG with amino or amino acid terminal groups PEG grafting ratio: 0.5% | ~60 | ~10 | / | / | [147] |
 PLN | DD90-C12-122: PEG-lipid 93:7 | i.v. | Cationic polymeric NPs, DD90-C12-122 | 159.5±36.3 | 16 | / | / | [148] |
 PLN | PBAE: DOPE: C18-PEG2000 75:20:5 | i.v. | PBAE Size | ~100 | / | / | Lung Endothelium Cells Lung Immune Cells | [149] |
 PLN | (DOTAP+PBAE): DOPE: Chol: DMG-PEG 50: 10: 38.5: 1.5 | i.v. | Vitronectin Positive charge | 100 | ~7 |  | Lung endothelium Cells | [150] |
 PLN | I-DD3: DOPE: Chol: C14-PEG2000 50: 25: 23.5: 1.5 | i.v. | Ionizable amino-polyesters I-DD3 | 100 ± 10 | 10.0 ± 2.1 | / | Lung endothelium Cells | [151] |
 PLN | AA03-DL-10: mDMG-PEG 9: 1 | i.v. | The 5-carbon spacer in the backbone of the lipomer and the 4 carbons on the side chain Clathrin-mediated endocytosis | 126 | -22.6 | / | / | [152] |
Active targeting | ||||||||
 LNP | MC3: DSPC: Chol: PEG-lipid 50: 10: 38.5: 1.5 Conjugated with mAb specific for PECAM-1 | i.v. | Active targeting (mAb specific for PECAM-1) | 103.3 ± 0.2 | -4.12 ± 0.1 | / | Lung endothelial cells | [153] |
 sLNP | MC3: DSPC: Chol: DMG-PEG: DSPE-PEG 50: 10: 38: 1.75: 0.25 Conjugated with αPV1 antibody | i.v. | Active targeting (αPV1 antibody) | 177 | -6.34 | / | Lung endothelial cells | [154] |