A cationic poly(2-oxazoline) with high in vitro transfection efficiency identified by a library approach.
To date, cationic polymers with high transfection efficiencies (TE) often have a high cytotoxicity. By screening an 18-membered library of cationic 2-oxazoline-based polymers, a polymer with similar TE as linear poly(ethylene imine) but no detectable cytotoxicity at the investigated concentrations could be identified. The influence of the polymer side chain hydrophobicity and the type and content of amino groups on the pDNA condensation, the TE, the cytotoxicity, the cellular membrane interaction as well as the size, charge, and stability of the polyplexes was studied. Primary amines and an amine content of at least 40% were required for an efficient TE. While polymers with short side chains were non-toxic up to an amine content of 40%, long hydrophobic side chains induced a high cytotoxicity.
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743, Jena, Germany.
Alexandra C
AC
Rinkenauer
Lutz
L
Tauhardt
Felix
F
Wendler
Kristian
K
Kempe
Michael
M
Gottschaldt
Anja
A
Traeger
Ulrich S
US
Schubert
D000588:Amines / Q000737:chemistry; D000818:Animals; D002412:Cations; D016923:Cell Death; D002850:Chromatography, Gel; D004996:Ethidium; D006461:Hemolysis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D010316:Particle Size; D066244:Proton Magnetic Resonance Spectroscopy; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014162:Transfection / Q000379:methods*
D000588:Amines; D002412:Cations; D010080:Oxazoles; D013438:Sulfhydryl Compounds; C577913:poly(2-oxazoline); D007770:L-Lactate Dehydrogenase; D004996:Ethidium
gene delivery; hydrophobic side chain; poly(2-oxazoline)s; primary amine; structure-property relationship; tertiary amine; viability