title: Design and biophysical characterization of bioresponsive degradable poly(dimethylaminoethyl methacrylate) based polymers for in vitro DNA transfection.
abstract: Water-soluble, degradable polymers based on poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with low cytotoxicity and good p-DNA transfection efficiency are highlighted in this article. To solve the nondegradability issue of PDMAEMA, new polymers based on DMAEMA and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) for gene transfection were synthesized. A poly(ethylene oxide) (PEO) azo-initiator was used as free-radical initiator. PEGylation was performed to improve water solubility and to reduce cytotoxicity of the polymers. The resulting polymers contain hydrolyzable ester linkages in the backbone and were soluble in water even with very high amounts of ester linkages. These degradable copolymers showed significantly less toxicity with a MTT assay using L929 cell lines and demonstrated promising DNA transfection efficiency when compared with the gold standard poly(ethyleneimine). Bioresponsive properties of the corresponding quaternized DMAEMA based degradable polymers were also studied. Although the quaternized DMAEMA copolymers showed enhanced water solubility, they were inferior in gene transfection and toxicity as compared to the unquaternized copolymers.
authors.affiliation: Department of Chemistry and Scientific Center for Materials Science,  Philipps-Universität Marburg , Hans-Meerwein Strasse, 35032 Marburg, Germany.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mengyao
authors.initials: M
authors.lastname: Zheng
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
authors.forename: Seema
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D018613:Microscopy, Confocal; D009757:Nylons / Q000138:chemical synthesis* / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000494:pharmacology; D012995:Solubility; D014162:Transfection; D014867:Water
chemical_list: D001672:Biocompatible Materials; D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D014867:Water; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA