Development of niucleic delivery system for targeting primary and metametastatic tumor

• Project/Area Number: 15K20831
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy; Biomedical engineering/Biomaterial science and engineering
• Research Institution: Hokkaido University
• Principal Investigator: SATO Yusuke 北海道大学, 薬学研究院, 助教 (10735624)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 脂質ナノ粒子 / 核酸送達 / 粒子径 / がん浸透性 / 動態制御 / siRNA / 薬物送達 / 粒径

Outline of Final Research Achievements

Limitation of diffusion of lipid nanoparticles (LNP) in tumor tissues is a severe problem for development of tumor-targeted short interfering RNA (siRNA) delivery system. In this research, to solve the problem, I developed a technology for controlling LNP size and elucidated the cause for a reduced efficiency of siRNA delivery, which is accompanied by downsizing of the siRNA-loaded LNPs.

Research Products

• [Journal Article] Innovative technologies in Nanomedicines: from passive targeting to active targeting/from controlled pharmacokinetics to controlled intracellular pharmacokinetics. (2017)
  • Author(s): Sato Y, Sakurai Y, Kajimoto K, Nakamura T, Yamada Y, Akita H, Harashima H.
  • Journal Title: Macromolecular Bioscience Volume: 17 Issue: 1 Pages: 1-16
  • DOI: 10.1002/mabi.201600179
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of a multifunctional envelope-type nano device and its application to nanomedicine. (2016)
  • Author(s): Sato Y, Nakamura T, Yamada Y, Harashima H.
  • Journal Title: J Control Release Volume: 244 Pages: 194-204
  • DOI: 10.1016/j.jconrel.2016.06.042
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] マイクロ流体デバイスによる脂質ナノ粒子作製とDDSへの応用 (2016)
  • Author(s): 真栄城正寿, 佐藤悠介, 原島秀吉, 渡慶次学
  • Journal Title: 機能材料 Volume: 36 Pages: 15-21
• [Journal Article] pH感受性脂質を基盤とした脂質ナノ粒子の開発と核酸ナノメディシンへの応用 (2016)
  • Author(s): 佐藤悠介, 原島秀吉
  • Journal Title: 化学工業 Volume: 67 Pages: 21-27
• [Journal Article] Elucidation of the physicochemical properties and potency of siRNA-loaded small-sized lipid nanoparticles for siRNA delivery (2016)
  • Author(s): Yusuke Sato, Yusuke Note, Masatoshi Maeki, Noritada Kaji, Yoshinobu Baba, Manabu Tokeshi, Hideyoshi Harashima
  • Journal Title: Journal of Controlled Release Volume: 229 Pages: 48-57
  • DOI: 10.1016/j.jconrel.2016.03.019
  • NAID: 120006219995
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Relationship Between the Physicochemical Properties of Lipid Nanoparticles and the Quality of siRNA Delivery to Liver Cells (2016)
  • Author(s): Yusuke Sato, Hiroto Hatakeyama, Mamoru Hyodo, Hideyoshi Harashima
  • Journal Title: Molecular Therapy Volume: 24 Issue: 4 Pages: 788-795
  • DOI: 10.1038/mt.2015.222
  • NAID: 120005906929
  • Peer Reviewed
• [Presentation] 肝臓標的型siRNA送達システムの安全性向上に関する検討 (2017)
  • Author(s): 佐藤里咲, 佐藤悠介, 松井秀樹, 原島秀吉
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-24
• [Presentation] メカニズムに基づいた安全性の高いsiRNA搭載脂質ナノ粒子の開発とB型肝炎治療への応用 (2017)
  • Author(s): 佐藤悠介, 松井秀樹, 佐藤里咲, 原島秀吉
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-24
• [Presentation] 肝臓を標的としたsiRNA搭載脂質ナノ粒子の物理化学的性質がsiRNA導入効率に及ぼす影響の評価 (2016)
  • Author(s): 佐藤悠介, 野手雄介, ショバキ ヌレ, 原島秀吉
  • Organizer: 第2回日本核酸医薬学会
  • Place of Presentation: 東京理科大学（東京都葛飾区）
  • Year and Date: 2016-11-15
• [Presentation] Optimizing siRNA delivery using specific multifunctional envelope-type nanodevice for liver sinusoidal endothelial cells (2016)
  • Author(s): Shobaki N, Sato Y, Harashima H
  • Organizer: AsiaNANO 2016: Asian Conference on Nanoscience and Nanotechnology
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2016-10-10
  • Int'l Joint Research
• [Presentation] Development of siRNA delivery system for the treatment of hepatitis B viral infection (2015)
  • Author(s): Yusuke Sato, Hiroto Hatakeyama, Naoki Yamamoto, Michinori Kohara, Hideyoshi Harashima
  • Organizer: The 18th Hokkaido University-Seoul National University Joint Sympojium
  • Place of Presentation: Seoul National University（韓国・ソウル）
  • Year and Date: 2015-11-26
  • Int'l Joint Research
• [Presentation] Elucidation of the physicochemical properties and potency for siRNA delivery of the siRNA-loaded small-sized nanoparticles (2015)
  • Author(s): Yusuke Note, Yusuke Sato, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
  • Organizer: The 18th Hokkaido University-Seoul National University Joint Sympojium
  • Place of Presentation: Seoul National University（韓国・ソウル）
  • Year and Date: 2015-11-26
  • Int'l Joint Research
• [Presentation] pH応答性脂質ナノ粒子による肝実質細胞選択的なsiRNA導入とB型肝炎治療 (2015)
  • Author(s): 佐藤悠介, 畠山浩人, 兵藤守, 山本直樹, 小原道法, 原島秀吉
  • Organizer: 第37回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 熊本大学（熊本県熊本市）
  • Year and Date: 2015-11-19