Ternary Complex of Plasmid DNA Electrostatically Assembled with Polyamidoamine Dendrimer and Chondroitin Sulfate for Effective and Secure Gene Delivery
スポンサーリンク
概要
- 論文の詳細を見る
The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with polyamidoamine (PAMAM) dendrimer and chondroitin sulfate (CS) for effective and secure gene delivery. PAMAM dendrimers are new cationic polymers that are expected to be used as gene delivery vectors. However, cationic non-viral gene vectors showed cytotoxicity by binding to negative cellular membranes. We therefore prepared a ternary complex by adding CS, an anionic polymer, and examined its usefulness. The pDNA/PAMAM dendrimer complex (PAMAM dendriplex) and the PAMAM dendriplex coated by CS (CS complex) showed nanoparticles with positive ζ- potential and negative ζ-potential, respectively. The CS complex had no cytotoxicity against B16-F10 cells and no agglutination activity, although severe cytotoxicity and high agglutination were observed in the PAMAM dendriplex. As a result of an in vitro gene expression study of B16-F10 cells, not only the PAMAM dendriplex but also the CS complex showed high transfection efficiency. The transfection efficiency of the CS complex was significantly inhibited by clathrinmediated endocytosis inhibitor (chlorpromazine), caveolae-mediated endocytosis inhibitor (genistein), and hypothermia. Tail-vein injection of the CS complex into mice led to significantly higher gene expression in the spleen than the PAMAM dendriplex. Thus, the ternary complex of pDNA electrostatically assembled with PAMAM denriplex and CS showed safe high gene expression in the spleen. This vector is expected to be useful for useful gene delivery.
- 日本薬学会の論文
- 2014-04-01
日本薬学会 | 論文
- Rapid and Sensitive Detection of Lophophora williamsii by Loop-Mediated Isothermal Amplification
- マウス摘出下部消化管におけるバニロイド受容体TRPV1の局在とカプサイシン誘起平滑筋収縮作用機序の解明 (生体機能と創薬シンポジウム2008--生命システムにおける情報ネットワークの重要性を解く 講演要旨集)
- NOを介する附子アルカロイド・メサコニチンの内皮依存性血管弛緩作用 (生体機能と創薬シンポジウム2007--創薬研究のルネサンスをめざして 講演要旨集) -- (シンポジウム 気体メディエーターと創薬)
- リンゴ未熟果由来プロアントシアニジンの食物アレルギー感作誘導抑制作用に関する研究 (第15回天然薬物の開発と応用シンポジウム講演要旨集) -- (一般講演)
- 新たな創薬ターゲットとしての膵β細胞機能調節因子 (生体機能と創薬シンポジウム2007--創薬研究のルネサンスをめざして 講演要旨集) -- (シンポジウム メタボリックシンドロームを巡る創薬)