Table 3.
Representatives of hybrid nanocarriers for the pulmonary delivery of DNA, mRNA, and siRNA.
| Nanocarriers | Composition | Size (nm) | Zeta potential (mV) | Mass median aerodynamic diameter (μm) | Encapsulation efficiency (w/w) (%) | Internalization efficiency/Transfection efficiency | Refs |
|---|---|---|---|---|---|---|---|
| pDNA | |||||||
| Polymer-peptide nanoparticles | Chitosan (126 kDa/mol) Fibronectin attachment protein of mycobacterium bovis (FAP-B) |
250 | −1 | – | – | After administration of FAP-B/CS-DNA NPs to BALB/c mice using an air-jet nebulizer, the transfection efficiency in the mouse lung was increased 16-fold compared with unmodified Chitosan NPs. | [211] |
| Polymer-peptide nanoparticles | PLGA (7–17 kDa) CPPs (They derived from lactoferrin and composed by 22 amino acids) |
167.9 | −0.13 | – | 96.7 | The internalization efficiencies of NPs were 83.85 ± 1.2% in Beas-2B cells and 96.76 ± 1.7% in A549 cells. | [207] |
| Lipid-polymer nanoparticles | Triolein PEI (1.2 kDa) DOPE |
228.1 | +11.92 | – | – | SPC-A1 cells (Human lung adenocarcinoma cells) were transfected in vitro. When N/P (The ratio of nitrogen in PEI to phosphate in DNA) was 10, the transfection efficiency of NPs was twice that of Lipofectamine 2000. | [212] |
| Polymer-peptide nanoparticles | DSPE-PEG2000 PBAEs PLGA CPP (mTAT/bPrPp/MPG) |
< 200 | +9.1 − +30.2 | – | – | CFBE41o cells were transfected in vitro. After 3 h, the transfection efficiency of Lipofectamine 2000 was approximately 4.5 times that of PBAEs/PLGA NPs. After 7 h, the transfection efficiency of bPrPp- or MPG-modified NPs was similar to that of Lipofectamine 2000. However, the transfection efficiency of mTAT-modified NPs was lower than that of PBAEs/PLGA NPs and Lipofectamine 2000. | [109] |
| Lipid-polymer nanoparticles | DOTAP DOPE Protamine sulfate salt Hyaluronic acid sodium salt |
207.8 | −13.1 | – | – | In A549 cells, the cellular uptake of HA-modified liposome-protamine-DNA nano-complex (LPD) was approximately 1.2 times that of LPD, and the gene silencing of HA-modified LPD was 2.5 times that of LPD. | [100] |
| mRNA | |||||||
| Polymer-peptide nanoparticles | KL4 peptide PEG12 (600 Da) |
432 (SD) 375 (SFD) |
+27.58 (SD) +30.58 (SFD) |
4.45/5.54 (SD) 1.53/2.13 (SFD) |
– | In vitro transfection of A549 cells, the transfection efficiency of HNPs was similar to that of Lipofectamine 2000. After intratracheal administration to the lung of BALB/c mice for 24 h, the transfection efficiency of PEG12KL4 NPs was 12-fold higher than that of Lipofectamine 2000 at a ratio of PEG12KL4 to mRNA of 10:1 (w/w). | [125] |
| siRNA | |||||||
| Lipid-polymer nanoparticles | PLGA (20 kDa) DOTAP (15 w/w) |
216 | +33.1 | 3.69 | – | H1299/EGFP cells (Human non-small cell lung carcinoma cell line stably expressing the reporter gene EGFP) were transfected in vitro. The gene silencing of HNPs was about 1/6 of that of Lipofectamine 2000. | [213] |
| Lipid-polymer nanoparticles | PLGA (7–17 kDa) DPPC |
141 | −29.1 | 3.96 | 74.8 | In vitro transfection of A549 cells resulted in gene silencing, and DPPC/PLGA NPs reduced the protein expression of aENaC and bENaC by 60% and 40%, respectively. | [204] |
| Polymer-peptide nanoparticles | Melittin (It inserts into lipid membranes and induces pores) p(OEGMA-DMAEMA) (Hydrophilic cation polymer) p(DIPAMA-PDSEMA) (pH-sensitive polymer that changes from hydrophobic to hydrophilic under acidic conditions) |
62 | +40.5 | – | – | When the N/P ratio was 8, the internalization efficiency of virus-inspired polymer for endosomal release (VIPER) in T lymphocytes was twice that of Lipofectamine 2000. H1299/EGFP cells were transfected in vitro. When the N/P ratio was 8 and 10, the gene silencing of VIPER was 4 times that of Lipofectamine 2000. When the N/P ratio was 8, the gene silencing was 76% after intratracheal administration to the lung of BALB/c mice for 24 h, which was approximately twice that of PEI. | [132,214] |
| Lipid-polymer nanoparticles | Lipidoid 5 (L5) (It is a novel cationic lipid consisting of an alkylated tetraamine backbone) PLGA (20 kDa) Cholesterol DOTAP N-palmitoyl-sphingosine-1-succinyl(methoxypolyethylene glycol 2000) (C16-PEG2000 ceramide) |
60–100 | 5–10 | – | 80–90 | The internalization efficiency of L5/C16-PEG2000/DOTAP/PLGA NPs in THP-1 cells (human macrophages) was approximately 4 times that of L5/DOTAP/PLGA NPs and 6 times that of DOTAP/PLGA NPs. However, the internalization efficiency of DOTAP/PLGA NPs in hAELVi cells (human ATI cells) was approximately 8.5 times higher than that of L5/C16-PEG2000/PLGA NPs. | [215] |