title: Calcium-activated gene transfection from DNA/poly(amic acid-co-imide) complexes.
abstract: In this study, we synthesized a water-soluble poly(amic acid-co-imide) (PA-I) from ethylenediaminetetraacetic dianhydride (EDTA) and 2,2'-(ethylenedioxy)bis(ethylamine) that possesses comparable transfection efficiency to that of polyethylenimine (PEI), when prepared in combination with divalent calcium cations. The polycondensation of monomers afforded poly(amic acid) (PA) precursors, and subsequent thermal imidization resulted in the formation of PA-I. At a polymer/DNA ratio (indicated by the molar ratio of nitrogen in the polymer to phosphate in DNA) of 40, complete retardation of the DNA band was observed by gel electrophoresis, indicating the strong association of DNA with PA-I. A zeta potential of -22 mV was recorded for the PA-I polymer solution, and no apparent cytotoxicity was observed at concentrations up to 500 μg·mL(-1). In the presence of divalent Ca(2+), the transfection efficiency of PA-I was higher than that of PA, due to the formation of a copolymer/Ca(2+)/DNA polyplex and the reduction in negative charge due to thermal cyclization. Interestingly, a synergistic effect of Ca(2+) and the synthesized copolymer on DNA transfection was observed. The use of Ca(2+) or copolymer alone resulted in unsatisfactory delivery, whereas the formation of three-component polyplexes synergistically increased DNA transfection. Our findings demonstrated that a PA-I/Ca(2+)/DNA polyplex could serve as a promising candidate for gene delivery.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan ; Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan ; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Biotechnology, Hungkuang University, Taichung, Taiwan.
authors.forename: Szu-Yuan
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Chang
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Sydeny
authors.initials: S
authors.lastname: Peng
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Tsai
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D007094:Imides / Q000737:chemistry / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D007094:Imides; D011108:Polymers; D004247:DNA; D002118:Calcium
keywords: gene carrier; poly(amic acid); polyimide