| Strategies for Improvement of PEG-vectors |
Examples |
Properties of Modified Vectors |
References |
| Substitution of PEG with other non-ionic, hydrophilic polymers |
Polysaccharides such as chitosan and dextran |
PEI-chitosan conjugate showed maximum luciferase activity in spleen followed by heart and brain in the mice after 7 days in comparison with branched PEI 25 kDa |
[27] |
| Dextran-spermine conjugate could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency in lung |
[28] |
| poly(N-vinyl-2-pyrrolidone) (PVP) |
PVP-coated nanoparticles instead of PEG can evade the accelerated blood clearance phenomenon |
[29] |
| Polyoxazolines (POZ) |
PLL-POZ can provide stability against serum compounds and enzymatic digestion as well as thermal stability |
[30] |
| N-(2-hydroxypropyl)methacrylamide (PHPMA) |
The alpha-half-life for bloodstream clearance of PLL or PEI/ DNA complexes could be extended using multivalent PHPMA coating |
[31] |
| pH-sensitive shielding of DNA polyplexes or lipoplexes |
PEG−acetal−MAL (maleimide moiety) |
The PEG−acetal−PEI conjugate had a half-life of 3 min at endosomal pH 5.5 and 2 h at physiological pH 7.4, respectively |
[32] |
| [ω-2-pyridyldithio poly (ethylene) glycol α-(butyraldehyde) (N(1)-cholesteryloxycarbonyl-1, 2-diaminoethane amidocarboxy) pyridylhydrazone]OPSS-PEG-HZN-Chol micelles |
OPSS-PEG-HZN-Chol micelles for shielding targeted PEI lipo-polyplexes remain stable at pH 7.4 at 37 °C. At endosomal pH 5.4, OPSS-PEG-HZN-Chol micelles are destroyed within 30 min at 37 °C, while OPSS-PEG-Chol micelles remain stable |
[33] |
| Using enzymatically cleavable PEG linkers |
PEG-peptide-DOPE (PPD) that is cleaved in a matrix metalloproteinase (MMP)-rich environment |
A multifunctional envelope-type nano device (MEND) that is modified with PPD showed no hepatotoxicity and innate immune stimulation. Also less accumulation in liver and spleen was observed PPD-MEND compared to the PEG-unmodified MEND |
[34] |
| Producing of reducible PEG nanoparticles |
PEG-ss-chitosan oligosaccharide-ss-polyethylenimine (PEG-ss-COS-ss-PEI) |
PEG-ss-COS-ss-PEI copolymers not only had much lower cytotoxicity, but also displayed high transfection efficiency as compared to the control branched PEI 25 kDa |
[35] |
