Comparison of random and gradient amino functionalized poly(2‐oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?. Issue 12 (18th April 2018)

• Record Type: Journal Article
• Authors: Hertz, David; Leiske, Meike N.; Wloka, Thomas; Traeger, Anja; Hartlieb, Matthias; Kessels, Michael M.; Schubert, Stephanie; Qualmann, Britta; Schubert, Ulrich S.
• Is Part Of: Journal of polymer science. Volume 56:Issue 12(2018)
• Page Start: 1210
• Page End: 1224
• Publication Date: 2018-04-18
• Subjects: cell uptake -- DNA interaction -- flow cytometry -- poly(2‐oxazoline) -- random and gradient copolymers; 547
• DOI: 10.1002/pola.29000
• Languages: English
• ISSNs: 0887-624X

Abstract

ABSTRACT: Poly(ethylene imine) can be considered as the gold standard for DNA delivery into cells in vitro, but severe cytotoxic side‐effects and inapplicability for targeted approaches in vivo urgently call for the design of new gene carriers. Since poly(2‐oxazoline)s (P(Ox)s) can be easily synthesized and modified, this polymer class might be ideal for the optimization of polymeric transfection processes. The utilization of 2‐methyl‐2‐oxazoline (MeOx) and 2‐ethyl‐2‐oxazoline (EtOx) is also known to be beneficial because these monomers were suggested to overcome solubility issues, mediate stealth behavior and, consequently, facilitate a reduction of cytotoxicity. A series of amino (AmOx) functionalized P(Ox) copolymers with either MeOx (gradient copolymers) or EtOx (random copolymers) was synthesized, deprotected and biochemically characterized regarding cytotoxicity, polyplex formation ability, cellular uptake, and transfection efficiency. Polymers with percentages of AmOx higher than 35 mol % showed stable polyplex formation and also an increase in cytotoxicity. All elucidated P(Ox)s revealed a poor transfection efficiency in both L929 and Hepa1‐6 cell lines. However, the investigations contribute to the understanding of the influence of stealth units (MeOx and EtOx) and their distribution within the polymer chain on selected properties of polyplexes and describe characteristics of amino functionalized P(Ox)s in different cell lines. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2018, 56, 1210–1224 Abstract : Gradient and random water‐soluble copolymers consisting of either 2‐methyl‐2‐oxazoline (MeOx) and 2‐aminobutyl‐2‐oxazoline (AmOx) (gradient copolymers) or 2‐ethyl‐2‐oxazoline (EtOx) and AmOx (random copolymers) are prepared using the cationic ring‐opening technique. Polymers with different AmOx contents are characterized and compared regarding their polyplex formation and dissociation ability as well as cytotoxicity, cellular uptake and transfection efficiency. This study compared L929 mouse fibroblasts with Hepa1‐6 murine liver cells in different cultivation media.