多糖・オリゴ核酸複合体を用いた抗原提示細胞への免疫刺激性CpG配列のデリバリー

2007 Fiscal Year Annual Research Report

• Project/Area Number: 16350068
• Research Institution: The University of Kitakyushu
• Principal Investigator: 櫻井 和朗 The University of Kitakyushu, 国際環境工学部, 教授 (70343431)
• Keywords: ナノゲル / 化学的架橋 / ナノサイズ / 抗原提示細胞 / MIFの過剰発現 / RAWとHEK / Anti-dectin-1抗体

Research Abstract

DDSの効率化を図るためにナノゲル作成の条件として、化学的架橋方法や粉砕方法を検討した。凍結乾燥した後に真空凍結乾燥して水分を完全に除去した綿状の乾燥物をボールミルで粉砕することによりナノサイズのゲル粒子を作成することに成功した。水分を完全に除去することが極めて大切であり、残存水分があると粒子径が大きくなり、ナノサイズの粒子が得られないことが判明した。さらに、dectin-1を介して特異的に抗原提示細胞に核酸医薬が送達され、MIFの過剰発現を抑えることをインビトロレベルで証明するために、dectin-1を強制発現している細胞(RAWとHEK)を入手して、核酸医薬の特異的な取り込みが起きるかを調べた。FITCを修飾したSPGやDNAの取り込みを、FACSを用いて検討した。Anti-dectin-1抗体で取り込みが抑制されたことから、根幹となるアイデアの正当性が証明された。

Research Products

• [Journal Article] Polysaccharide-Templated Twisted Assemble of 2-Anilinonaphthalene-6-sulfonic Acid. (2008)
  • Author(s): Naohiko Shimada, Yoichi Takeda, Seiji Shinkai, Kazuo Sakurai.
  • Journal Title: J.Polymer Science Part A. Pages: 1440-1448
  • Peer Reviewed
• [Journal Article] Clustered CpG Sequences to Enhance Cytokine Secretion from Macrophages. (2008)
  • Author(s): Jusaku Minari, Naohiko Shimada, and Kazuo Sakurai
  • Journal Title: Chemistry Letters. Pages: 92-93
  • Peer Reviewed
• [Journal Article] Intramolecular cation-pai interactions control the conformation of nonrestricted(phenylalkyl)pyridinesw. (2008)
  • Author(s): Isabella Richter, Jusaku Minari, Philip Axe, John P. Lowe, Tony D. James, Kazuo Sakurai, Steven D. Bull and John S. Fossey.
  • Journal Title: ChemComm. Pages: 1082-1084
  • Peer Reviewed
• [Journal Article] Molecular Dynamics Studies of Side Chain Effect on the β-1,3-D-Glucan Triple Helix in Aqueous Solution. (2008)
  • Author(s): Okobira, T.; Miyoshi, K.; Uezu, K.; Sakurai, K.; Shinkai, S.
  • Journal Title: Biomacromolecules 9(3) Pages: 783-788
  • Peer Reviewed
• [Journal Article] Entrapment of Immature Amyloid Protofilaments in the Hydrophobic Domain of Schizophyllan. (2008)
  • Author(s): Sakuragi, M.; Takeda, Y.; Shimada, N.; Sakurai, K.
  • Journal Title: Polymer Bulletin accepted
  • Peer Reviewed
• [Journal Article] Complex Made from N,N-Bis(carboxymethyl)Glutamate Tetrasodium Salt and Sodium Oleate that Forms a Highly Ordered Lamella in Gel Phase. (2007)
  • Author(s): Jeong, Y., Uezu. K, Sakurai, S., Masunaga, H., Inoue, K., Sasaki, S., Shimada, N., Takeda, Y., Kaneko, K. and Sakurai, K.
  • Journal Title: Bull.Chem.Soc.Jpn. 80(2) Pages: 410-417
  • Peer Reviewed
• [Journal Article] Ternary Complex Consisting of DNA,Polycation,and a Natural Polysaccharide of Schizophyllan to Induce Cellular Uptake by Antigen Presenting Cells. (2007)
  • Author(s): Yoichi Takeda, Naohiko Shimada, Kenji Kaneko, Seiji Shinkai, and Kazuo Sakurai.
  • Journal Title: Biomacromolecules 2(3) Pages: 641-650
  • Peer Reviewed
• [Journal Article] DNA Conformational Switching by Use of an Intercalator and Its Receptor. (2007)
  • Author(s): Tomoki Nishimura, Yoichi Takeda, Naohiko Shimada, and Kazuo Sakurail.
  • Journal Title: Chemistry Letters 36(3) Pages: 388-389
  • Peer Reviewed
• [Journal Article] Instantaneous Inclusion of a Polynucleotide and Hydrophobic Guest Molecules into a Helical Core of Cationic -1,3-Glucan Polysaccharide. (2007)
  • Author(s): Ikeda, M.; Hasegawa, T.; Numata, M.; Sugikawa, K.; Sakurai, K.; Fujiki, M.; Shinkai, S.
  • Journal Title: J.Am.Chem.Soc 129(13) Pages: 3979-3988
  • Peer Reviewed
• [Journal Article] Salt-Concentration Dependence of the Structure and Form Factors for the Wormlike-Micelle Made from LES/AMPB Dual-Surfactant in Aqueous Solution. (2007)
  • Author(s): Kenichi Eguchi, Isamu Kaneda, Yoshiko Hiwatari, Hiroyasu Masunagac and Kazuo Sakurai.
  • Journal Title: J.Applied Crystallography 40 Pages: 264-268
  • Peer Reviewed
• [Journal Article] A Polysaccharide Carrier to Effectively Deliver Native Phosphodiester CpG DNA to APCs. (2007)
  • Author(s): Naohiko Shimada, Cevayir Coban, Yoichi Takeda, Masami Mizu, Jusaku Minari, Takahisa Anada, Yuichi Torii, Seiji Shinkai, Shizuo Akira, Ken J. Ishii, Kazuo Sakurai.
  • Journal Title: Bioconjugate Chem. 17(5) Pages: 1136-1140
  • Peer Reviewed
• [Journal Article] Delivery of Antisense Oligonucleotides to Nuclear Telomere RNA by Use of a Complex between Polysaccharide and Polynucleotide. (2007)
  • Author(s): Jusaku Minari, Takanori Kubo, Hideki Ohba, Naohiko Shimada, Yoich Takeda, Ryouji Karinaga, Takahisa Anada, Kazuya Koumoto, Takeshi Kawazu, Takeshi Nagasaki, Seiji Shinkai, and Kazuo Sakurai.
  • Journal Title: Bull.Chem.Soc.Jpn. 80(6) Pages: 1091-1098
  • Peer Reviewed
• [Journal Article] DNA Binding of Tilorone;1H NMR and Calorimetric Studies of the Intercalation. (2007)
  • Author(s): Tomoki Nishimura, Naohiko Shimada, Yoichi Takeda, and Kazuo Sakurai.
  • Journal Title: Biochemistry 46 Pages: 8156-8163
  • Peer Reviewed
• [Presentation] DDS粒子内のDNAの折りたたみ構造と効率の関係 (2008)
  • Author(s): 櫻井 和朗
  • Organizer: 東京大学新領域創成科学研究科セミナー
  • Place of Presentation: 東京大学
  • Year and Date: 2008-03-07
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 化学的アプローチを利用したCpG DNAによる免疫応答の制御 (2007)
  • Author(s): 三成 寿作
  • Organizer: 第17回アンチセンスシンポジウム
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 20071203-04
• [Presentation] 抗原提示細胞上のDectinelを標的とした核酸医薬のDDS (2007)
  • Author(s): 櫻井 和朗
  • Organizer: 第56回高分子学会討論会にて
  • Place of Presentation: 名古屋工業大学
  • Year and Date: 2007-09-20
• [Presentation] 極性基を有す温度応答性デンドロンの分子集合体形成 (2007)
  • Author(s): 西村 智貴
  • Organizer: 第56回高分子学会討論会にて
  • Place of Presentation: 名古屋工業大学
  • Year and Date: 2007-09-19
• [Presentation] A Novel Cationic Lipid to Delivery DNA-Relationship between chemistry,biological function and nanostructure (2007)
  • Author(s): 櫻井 和朗
  • Organizer: RCSセミナー
  • Place of Presentation: Bath大学(イギリス)
  • Year and Date: 2007-08-17