title: Reducible poly(2-dimethylaminoethyl methacrylate): synthesis, cytotoxicity, and gene delivery activity.
abstract: Reducible polycations represent promising carriers of therapeutic nucleic acids. Oligomers of 2-dimethylaminoethyl methacrylate (DMAEMA) containing terminal thiol groups were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using difunctional chain transfer agent. Reducible poly(DMAEMA) (rPDMAEMA) was synthesized by oxidation of the terminal thiol groups, forming a polymer with disulfide bonds in the backbone. Physico-chemical properties of DNA polyplexes of rPDMAEMA were evaluated by dynamic and static light scattering methods, revealing lower structural density and DNA content than control PDMAEMA polyplexes. Cytotoxicity and transfection activity of rPDMAEMA-based DNA polyplexes were evaluated in vitro. In comparison with control PDMAEMA, only minimum toxic effects of rPDMAEMA were observed in a panel of cell lines. Transfection activity was tested in B16F10 mouse melanoma and six human pancreatic cancer cell lines. rPDMAEMA polyplexes showed a comparable or better activity than control PDMAEMA polyplexes.
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Ye-Zi
authors.initials: YZ
authors.lastname: You
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Devika Soundara
authors.initials: DS
authors.lastname: Manickam
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: David
authors.initials: D
authors.lastname: Oupický
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage; D004337:Drug Carriers / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008689:Methacrylates / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D009757:Nylons / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D014162:Transfection
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D004247:DNA; D008156:Luciferases