Table 2.
Mechanism of cellular uptake and endosomal escape for charge-reversing nucleic acid delivery systems
| System Name | Encapsulated Nucleic Acid | Uptake Mechanism | Escape Mechanism | Release Stage | References |
|---|---|---|---|---|---|
| Poly(N-(N’-[(N”-cis-aconityl)-2-aminoethyl]-2-aminoethyl)aspartamide) [(pAsp(DET-Aco)]; Poly(N-[N’-(2-aminoethyl)-2-aminoethyl]aspartamide) [pAsp(DET)] | pDNA | Endocytosis | Endosome disruption (Membrane destabilization) | Endosome | Angew. Chem. Int. Ed. 2008, 407, 5163–5166 |
| Lipid-like amphiphile with ammonium headgroup and benzyl ester terminated lipophilic acyl chains | pDNA for β-gal, GFP encoding DNA | Macropinocytosis | - | - | J. Am. Chem. Soc. 2004, 126, 39, 12196–12197; Mol. Pharmaceutics 2011, 8, 758–766 |
| Poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] [B-PDEAEA] coated with DOPE and DC-Chol lipids | DNA | Clathrin-mediated endocytosis | Endosomal disruption by fusogenic DOPE (presumably) | Lysosome | Adv. Mater. 2016, 28, 1743–1752 |
| Polymer with quaternary amines carrying N-propionic 4-acetoxybenzyl ester | pLUCI pTRAIL |
Endocytosis | Endosomal disruption by fusogenic DOPE (presumably) | Lysosome | Adv. Mater. 2016, 28, 10613–10622 |
| Oligo(carbonate-b-α-amino ester) [CART] | EGFP mRNA |
Endocytosis | Osmotic rupture | Endosome | PNAS 114, no. 4 (2017): E448-E456. |
| Poly(N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N,N-diethylammonium chloride) [PQDEA] | pLUCI pTRAIL |
Clathrin-mediated endocytosis | Osmotic swelling | Lysosome | Biomacromolecules 2018, 19, 2308–2319 |
| DNA-grafted polycaprolactone [DNA-g-PCL] | siRNA | Endocytosis | - | Early/Late Endosome | Angew. Chem. Int. Ed. 2018, 57, 3064–3068 |
| Hyaluronic acid- ethylenimine [HA-PEI] | siRNA | Receptor mediated endocytosis via HA-CD44 interaction | ATP dependent endosomolysis | Endo/Lysosome | Biomacromolecules 2018, 19, 3776–3787 |
| PEI-FPBA-Chol-Dopa micelle [PFCDM] | siRNA | Endocytosis | ATP dependent endosomolysis (presumably) | Endo/Lysosome | ACS Appl. Mater. Interfaces 2018, 10, 32026–32037 |
| Propiolic acid decorated cationic lipid LG2C14 | siRNA | Macropintocytosis and Clathrin-mediated pathways | Membrane fusion | Endo/Lysosome | Biomater. Sci., 2018, 6, 3075–3084 |
| Poly(pyridyldisulfide-dodecyl methacrylate) coated with DOPE-DSPE/PEG lipids [L-siP] | siRNA | Macropinocytosis and Clathrin-mediated endocytosis | Endosomal disruption by fusogenic DOPE | Endosome | ACS Appl. Mater. Interfaces 2019, 11, 24971–24983 |
| Poly[3-aminopropylmethacrylamide-co-N,N-(dimethylamino)ethylacrylate] [PAD] | DNA | Endocytosis | pH buffering and disruption of endosomal membrane | Endosome | ACS Omega 2020, 5, 9114–9122 |
| Polybutadiene-b-poly(methacrylic acid)-b-poly(2-(dimethylamino)ethyl methacrylate) [(BMAAD)] | pDNA | Endocytosis | Particle swelling followed by membrane disruption | Endosome | ACS nano, 2013, 7(11), pp.9621–9631 |