title: Novel redox nanomedicine improves gene expression of polyion complex vector.
abstract: Gene therapy has generated worldwide attention as a new medical technology. While non-viral gene vectors are promising candidates as gene carriers, they have several issues such as toxicity and low transfection efficiency. We have hypothesized that the generation of reactive oxygen species (ROS) affects gene expression in polyplex supported gene delivery systems. The effect of ROS on the gene expression of polyplex was evaluated using a nitroxide radical-containing nanoparticle (RNP) as an ROS scavenger. When polyethyleneimine (PEI)/pGL3 or PEI alone was added to the HeLa cells, ROS levels increased significantly. In contrast, when (PEI)/pGL3 or PEI was added with RNP, the ROS levels were suppressed. The luciferase expression was increased by the treatment with RNP in a dose-dependent manner and the cellular uptake of pDNA was also increased. Inflammatory cytokines play an important role in ROS generationin vivo. In particular, tumor necrosis factor (TNF)-α caused intracellular ROS generation in HeLa cells and decreased gene expression. RNP treatment suppressed ROS production even in the presence of TNF-α and increased gene expression. This anti-inflammatory property of RNP suggests that it may be used as an effective adjuvant for non-viral gene delivery systems.
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Toh
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yoshitomi
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (MANA), National Institute of Materials Science (NIMS), Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
keywords: anti-inflammation; nitroxide radical-containing nanoparticle; non-viral gene delivery system; polyplex; reactive oxygen species