Development of nanoparticles including anti-inflammatory phospholipids for novel treatment strategy of vascular diseases

• Project/Area Number: 17K10748
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: The University of Tokyo
• Principal Investigator: AKAGI DAISUKE 東京大学, 医学部附属病院, 特任研究員 (20464753)
• Co-Investigator(Kenkyū-buntansha): 山本 晃太 東京大学, 医学部附属病院, 登録研究員 (00753542) ; 保科 克行 東京大学, 医学部附属病院, 講師 (90571761) ; 渡邉 聡明 東京大学, 医学部附属病院, 教授 (80210920)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ナノ粒子 / 抗炎症作用 / 内膜肥厚 / 血管外科 / Drug delivery system / ミセル型ベクター / 抗炎症脂質 / 核酸医薬 / ナノテクノロジー / ナノマテリアル / ドラッグデリバリーシステム / 血管傷害 / 外科 / 脂質 / ナノマシン / 循環器・高血圧 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Neontimal hyperplasia caused by bypass surgery or endovascular treatment is a major problem that impairs therapeutic results such as patency of the graft.The basic mechanism is inflammation. To control this, nanovectors containing an anti-inflammatory lipid were prepared and examined. In addition, we also prepared nanovectors containing nuclear acid which shows an anti-inflammatory effect were also prepared and examined. We showed an anti-inflammatory effect of these nanovectors on smooth muscle cells. In animal models with neointimal hyperplasia they are showing to suppress neointimal hyperplasia.

Academic Significance and Societal Importance of the Research Achievements

血管外科治療後内膜肥厚の制御法は画期的な方法がなく現在も様々な薬をはじめとする治療法が開発中である。本研究は、抗炎症作用に注目した新規創薬／新たなドラッグデリバリーシステム（DDS）構築などの基礎となるものであり、内膜肥厚制御システムの確立に大きく前進するのみならず、炎症性疾患一般の制御に応用可能性があり意義が高い。

Research Products

• [Journal Article] Proresolving Lipid Mediators Resolvin D1 and Protectin D1 Isomer Attenuate Neointimal Hyperplasia in the Rat Carotid Artery Balloon Injury Model. (2019)
  • Author(s): Makino Y, Miyahara T, Nitta J, Miyahara K, Seo A, Kimura M, Suhara M, Akai A, Akagi D, Yamamoto K, Hoshina K.
  • Journal Title: Journal of Surgical Research Volume: 233 Pages: 104-110
  • DOI: 10.1016/j.jss.2018.07.049
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between medical expenses and the severity of peripheral arterial disease in Japan (2018)
  • Author(s): Seo Akihiko、Yamamoto Kota、Akai Atsushi、Akagi Daisuke、Takayama Toshio、Hoshina Katsuyuki
  • Journal Title: Heart and Vessels Volume: 33 Issue: 8 Pages: 853-858
  • DOI: 10.1007/s00380-018-1127-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size (2018)
  • Author(s): Suhara Masamitsu、Miura Yutaka、Cabral Horacio、Akagi Daisuke、Anraku Yasutaka、Kishimura Akihiro、Sano Masaya、Miyazaki Takuya、Nakamura Noriko、Nishiyama Ayako、Kataoka Kazunori、Koyama Hiroyuki、Hoshina Katsuyuki
  • Journal Title: Journal of Controlled Release Volume: 286 Pages: 394-401
  • DOI: 10.1016/j.jconrel.2018.07.049
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 血行再建術後内膜肥厚機構と抗炎症作用による制御システムの構築 (2019)
  • Author(s): 赤木大輔、保科克行、Michael S Conte
  • Organizer: 第60回日本脈管学会総会
• [Presentation] 血管炎による末梢動脈閉塞の治療戦略 (2019)
  • Author(s): 赤木大輔、根元洋光
  • Organizer: 第60回日本脈管学会総会
• [Presentation] 核酸を用いた安定的DDSによる 血行再建後内膜肥厚制御構築の試み (2019)
  • Author(s): 佐野允哉、赤木大輔、大片慎也 、花田和正、松浦壮平 、大橋雄一、 宮原和洋 、福原菜摘、赤井隆文、伊佐治寿彦、 高山利夫 、内藤瑞、宮田完二郎、保科克行
  • Organizer: 第60回日本脈管学会総会