Table 2.
Some nonviral nanosystems for mRNA delivery in Section 5.
| Category | Key Component | Core Technology | Size (nm) | Delivery Route | Gene | Ref |
| LNPs | Ionizable lipids, DOPE, C14-PEG2000 | Heterocyclic lipids formed by one-step three-component reaction (3-CR) |
100 | In vitro i.m. (mouse) |
Fluc | [75] |
| LNPs | DOPE, DSPC, PEG ionizable lipids |
Helper lipid structure | 170.5/167.2 | i.v. (mouse) | Fluc | [78] |
| LNPs | C14–4, DOPE, Chol PEG |
Optimized ratios in LNPs | 57–151 | In vitro | Luc | [81] |
| LNPs | Ionizable lipid, cholesterol, DSPC, DMPE-PEG | Optimized molar ratio between ionizable lipids and mRNA | 82–90 | In vitro | Human erythropoietin | [96] |
| LNPs | Synthesized lipid, DOPE, cholesterol, DMG-PEG2k | Lipid with unsaturated tail | 143 | In vitro i.v. (mouse) |
Fluc | [97] |
| LNPs | DSPC, cholesterol, MC3, PEG2k-DMG | Generated via stepwise ethanol dilution | 61 | i.v. (rat) i.v. (monkey) |
hEPO | [88] |
| LNPs | Cationic lipids, DSPE-PEG 2000 |
Optimized cationic lipid-like materials | 140–160 | DC-mediated (mouse) |
OVA | [89] |
| Polymers | Ionizable lipids, phospholipids, PEG, cholesterol |
Ionizable amphiphilic Janus dendrimer (IAJD) | 75/92 | In vitro i.p. (mouse) |
Luc | [119] |
| Polymers | Alginate, chitosan | Hydrogels | Not mentioned | In vitro | hGLuc | [122] |
| Polymers | Chitosan, hyaluronic acid, trehalose | Hydrogels | 80–180 | In vitro | Luc | [124] |
| Polymers | PLGA, PEI | Nontoxic PLGA | 428.9 ± 12 | DC-based | GFP | [126] |
| Polymers | PEG | Cation-free delivery strategy with PEG | 10–90 | In vitro | GLuc | [127] |
| Polypeptide | Protamine | Natural cationic peptide | 90–180 | In vitro | Luc | [128] |
| Polypeptide | Protamine | Natural cationic peptide | 30–110 | i.d. (human) | TAA for NSCLC | [130] |
| Polypeptide | Pepfect14 | Cationic CPP | 70–110 | i.p. (3D model) | eGFP mCherry |
[134] |
| Polypeptide | RALA CPP | Arginine-rich peptide | 89–144 | In vitro i.v. (mouse) |
eGFP OVA |
[135] |
| Hybrid | Protamine, DOTAP | Heterogenous internal organization | 146–234 | In vitro; i.m. (mouse) |
Luc | [141] |
| Hybrid | PLGA, DOTMA | Lipid-coated PLGA | 231 ± 7.0 | DC-based | m-cherry | [142] |
| Hybrid | PBAE, PEG-lipid | PBAE terpolymers formulated with PEG-lipid | 200–370 | i.v. (mouse) | Luc | [143] |
| Hybrid | Lipid, PLGA | adjuvant-loaded hybrid | 300 | DC-based i.v. (mouse) |
EGFP | [144] |
| Hybrid | DP-7, DOTAP, cholesterol |
DP7-C with double functions | 100.23 ± 7.5 | In vitro i.v./s.c. (mouse) |
eGFP neoantigen |
[145] |
| Polypeptide | PLA-NP, LAH4-L1 | Cationic CPP | 220.1 ± 22.9 | In vitro | eGFP | [146] |
| Polypeptide | PEG, KL4 peptide | Monodisperse linear PEG with peptide | 467.9 ± 24.9 | In vitro i.n. (mouse) |
eGFP | [147] |
| AuNP–DNA conjugates | AuNP, DNA | Targeted DNA | Not mentioned | In vitro s.c. (mouse) |
BAX GFP |
[159] |
| Exosome | Exosome | HEK-293F derived Exo | 120 ± 50 | i.m. (mouse) | Antares2 | [167] |
| Exosome | Exosome, EVHB | HER2-targeted peptide | Not mentioned | i.p. (mouse) | HChrR6 | [168] |
| Exosome | Exosomes | Exosome derived from RBC devoid of DNA | 100–250 | In vitro i.p., i.t. (mouse) |
125b ASO | [173] |