Development of a microRNA delivery system for cancer therapy

• Project/Area Number: 22790143
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: HATAKEYAMA Hiroto 北海道大学, 大学院・薬学研究院, 特任助教 (70504786)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ドラッグデリバリー / 核酸医薬 / がん治療 / miRNA / siRNA / anti-miRNA oligo / 多機能性エンベロープ型ナノ構造体 / 癌治療

Research Abstract

Because miRNA/anti-miRNA oligonucleotide(AMO) are considered to be a potential therapeutic tool for cancer, the aim of the study is to development of AMO delivery system based on lipid nanoparticels(NPs). miRNA/AMO were successfully encapsulated in NPs. The systemic administration of NPs modified with functional device for improving intracellular trafficking could induce anti-tumor effect in in vivo tumor-bearing mice model

Research Products

• [Journal Article] Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA (2011)
  • Author(s): 櫻井遊
  • Journal Title: Biomaterials Volume: 32 Issue: 24 Pages: 5733-5742
  • DOI: 10.1016/j.biomaterials.2011.04.047
  • Peer Reviewed
• [Journal Article] Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid (2011)
  • Author(s): Hatakeyama H, Akita H, Ito E, Hayashi Y, Oishi M, Nagasaki Y, Danev R, Nagayama K, Kaji N, Kikuchi H, Baba Y, Harashima H
  • Journal Title: Biomaterials Volume: 32 Issue: 8 Pages: 4306-4316
  • DOI: 10.1038/mt.2011.24
  • Peer Reviewed
• [Journal Article] A multifunctional envelope type nano device(MEND) for drug and gene delivery to tumors based on the EPR effect : a strategy for overcoming the PEG dilemma (2011)
  • Author(s): Hatakeyama H, Akita H, Harashima H
  • Journal Title: Adv. Drug Deliv. Rev. Volume: 63 Issue: 3 Pages: 152-160
  • DOI: 10.1016/j.addr.2010.09.001
  • Peer Reviewed
• [Journal Article] siRNAキャリアーとしてのリポソームの現状と将来 (2011)
  • Author(s): 楠本憲司、畠山浩人、原島秀吉
  • Journal Title: ファルマシア Volume: 47(8) Pages: 719-723
  • NAID: 110009884963
• [Journal Article] Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid (2011)
  • Author(s): Hatakeyama H
  • Journal Title: Biomaterials Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] A multifunctional envelope type nano device (MEND) for drug and gene delivery to tumors based on the EPR effect : a strategy for overcoming the PEG dilemma (2011)
  • Author(s): Hatakeyama H
  • Journal Title: Advanced Drug Delivery Review Volume: 63 Pages: 152-160
  • Peer Reviewed
• [Journal Article] Ornithine and tryptophan analogs as efficient polycations for siRNA delivery to tumor cells (2010)
  • Author(s): Sato Y, Hatakeyama H, Harashima H
  • Journal Title: Biol. Pharm. Bull. Volume: 33(7) Pages: 1246-1249
  • Peer Reviewed
• [Journal Article] A Novel Nonviral Gene Delivery System : Multifunctional Envelope-Type Nano Device (2010)
  • Author(s): Hatakeyama H, Akita H, Kogure K, Harashima H.
  • Journal Title: Adv. Biochem. Eng. Biotechnol. Volume: 119 Pages: 197-230
  • DOI: 10.1007/10_2008_40
  • ISBN: 9783642149467, 9783642149474
  • Peer Reviewed
• [Journal Article] siRNA delivery by multifunctional envelope-type nano device (MEND) (2010)
  • Author(s): 秋田英万、畠山浩人、原島秀吉
  • Journal Title: Drug Delivery System Volume: 25 Issue: 6 Pages: 590-597
  • DOI: 10.2745/dds.25.590
  • NAID: 10027642874
  • ISSN: 0913-5006, 1881-2732
• [Presentation] siRNA搭載pH応答性MENDの構築とin vivoへの応用 (2012)
  • Author(s): 佐藤悠介、畠山浩人、櫻井遊、兵藤守、秋田英万、原島秀吉
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2012-03-30
• [Presentation] siRNA搭載pH応答性MENDの構築とin vivoへの応用 (2012)
  • Author(s): 佐藤悠介、畠山浩人, 他
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌)(招待講演)
  • Year and Date: 2012-03-30
• [Presentation] 細胞内動態制御に基づくin vivo siRNAデリバリー技術の構築 (2011)
  • Author(s): 櫻井遊、畠山浩人、秋田英万、原島秀吉
  • Organizer: 薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2011-05-31
• [Presentation] 細胞内動態制御に基づくin vivo siRNAデリバリー技術の構築 (2011)
  • Author(s): 櫻井遊、畠山浩人, 他
  • Organizer: 薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京)(招待講演)
  • Year and Date: 2011-05-31
• [Presentation] pH変化に応答するsiRNA封入MENDの構築 (2011)
  • Author(s): 佐藤悠介、畠山浩人、秋田英万、兵藤守、原島秀吉
  • Organizer: 薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2011-05-29
• [Presentation] 腫瘍選択的siRNAデリバリーシステムの開発 (2011)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2011-05-29
• [Presentation] 腫瘍選択的siRNAデリバリーシステムの開発 (2011)
  • Author(s): 畠山浩人, 他
  • Organizer: 薬剤学会第26年会
  • Place of Presentation: タワーホール船堀(東京)(招待講演)
  • Year and Date: 2011-05-29
• [Presentation] Endosomal Escape of liposomal siRNA via membrane fusion and in vivo delivery to tumor (2011)
  • Author(s): Sakurai Y, Hatakeyama H, Sato Y, Akita H, Harashima H
  • Organizer: 7th annual meeting of the Oligonucleotide Therapeutics Society
  • Place of Presentation: The Black Diamond at The Royal Library Copenhagen(Denmark)
• [Presentation] In vivo siRNA delivery with pH-sensitive liposome (2011)
  • Author(s): Sato Y, Hatakeyama H, Sakurai Y, Hyodo M, Akita H, Harashima H
  • Organizer: 7th annual meeting of the Oligonucleotide Therapeutics Society
  • Place of Presentation: The Black Diamond at The Royal Library Copenhagen(Denmark)
• [Presentation] pH応答性膜融合性ペプチドを用いた腫瘍組織へのin vivo siRNAデリバリー技術の構築 (2011)
  • Author(s): 櫻井遊、畠山浩人、秋田英万、二木史朗、原島秀吉
  • Organizer: 遺伝子デリバリー研究会第11回夏期セミナー
  • Place of Presentation: 三翠園ホテル(高知)
• [Presentation] In vivo siRNA delivery with pH-sensitive liposome (2011)
  • Author(s): Sato Y, Hatakeyama H, et al
  • Organizer: 7th annual meeting of the Oligonucleotide Therapeutics Society
  • Place of Presentation: The Black Diamond at The Royal Library Copenhagen (Denmark)
• [Presentation] Endosomal Escape of liposomal siRNA via membrane fusion and in vivo delivery to tumor (2011)
  • Author(s): Sakurai Y, Hatakeyama H, et al
  • Organizer: 7th annual meeting of the Oligonucleotide Therapeutics Society
  • Place of Presentation: The Black Diamond at The Royal Library Copenhagen (Denmark)
• [Presentation] エンドソーム脱出素子を搭載したsiRNAデリバリーシステムの開発 (2010)
  • Author(s): 櫻井遊、畠山浩人, 他
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山、富山国際会議場
  • Year and Date: 2010-11-30
• [Presentation] 多機能性エンベロープ型ナノ構造体によるsiRNAの送達制御 (2010)
  • Author(s): 原島秀吉、秋田英万、畠山浩人
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山、富山国際会議場(招待講演)
  • Year and Date: 2010-11-29
• [Presentation] Development of systemic siRNA delivery system : manipulation of intracellular trafficking (2010)
  • Author(s): Hatakeyama H
  • Organizer: 13 the JOINT Hokkaido University-Seoul national University SYMPOSIUM
  • Place of Presentation: 北海道大学(札幌市)
  • Year and Date: 2010-11-26
• [Presentation] Development of systemic siRNA delivery system : manipulation of intracellular trafficking (2010)
  • Author(s): Hatakeyama H
  • Organizer: 13 the JOINT Hokkaido University-Seoul national University SYMPOSIUM
  • Place of Presentation: Sapporo, Hokkaido University(招待講演)
  • Year and Date: 2010-11-26
• [Presentation] Development of Systemic siRNA Delivery System for Tumor with endosomal escape device (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪
  • Year and Date: 2010-09-23
• [Presentation] Development of Systemic siRNA Delivery System for Tumor with endosomal escape device (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] Development of siRNA-containing nanoparticles for in vitro and in vivo gene silencing in tumor by controlling intracellular trafficking (2010)
  • Author(s): Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H
  • Organizer: 12th LIPOSOME RESEARCH DAYS CONFERENCE
  • Place of Presentation: The University of British Columbia(Canada)
  • Year and Date: 2010-08-04
• [Presentation] Development of siRNA-containing nanoparticles for in vitro and in vivo gene silencing in tumor by controlling intracellular trafficking (2010)
  • Author(s): Hatakeyama H, et al.
  • Organizer: 12th LIPOSOME RESEARCH DAYS CONFERENCE
  • Place of Presentation: Marriott Wardman Park Hotel, Washington DC, USA
  • Year and Date: 2010-08-04
• [Presentation] 腫瘍を標的とする革新的なin vivo siRNAデリバリーシステムの構築 (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪国際交流センター(大阪)
  • Year and Date: 2010-06-18
• [Presentation] 腫瘍を標的とする革新的なin vivo siRNAデリバリーシステムの構築 (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪、大阪国際交流センター(招待講演)
  • Year and Date: 2010-06-18
• [Presentation] siRNA封入MENDのエンドソーム脱出促進とin vivoがんへのデリバリー (2010)
  • Author(s): 櫻井遊、畠山浩人、秋田英万、二木史朗、原島秀吉
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪国際交流センター(大阪)
  • Year and Date: 2010-06-17
• [Presentation] Ornithine and tryptophan as an efficient polycation for siRNA delivery to tumor cells (2010)
  • Author(s): Sato Y, Hatakeyama H, Harashima H
  • Organizer: The 13th Annual Meeting of the American Society of Gene Therapy
  • Place of Presentation: Marriott Wardman Park Hotel(USA)
  • Year and Date: 2010-05-22
• [Presentation] Application of siRNA-containing nanoparticles for in vitro and in vivo gene silencing in tumor by controlling intracellular trafficking (2010)
  • Author(s): Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H
  • Organizer: The 13th Annual Meeting of the American Society of Gene and Cell Therapy
  • Place of Presentation: Marriott Wardman Park Hotel(USA)
  • Year and Date: 2010-05-20
• [Presentation] A pH-sensitive fusogenic peptide modified siRNA-encapsulating nanoparticles exerts the gene silencing synergistically with tumor-specific cleavable PEG-lipid (2010)
  • Author(s): Sakurai Y, Hatakeyama H, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H
  • Organizer: The 13th Annual Meeting of the American Society of Gene Therapy
  • Place of Presentation: Marriott Wardman Park Hotel(USA)
  • Year and Date: 2010-05-20
• [Presentation] Application of siRNA-containing nanoparticles for in vitro and in vivo gene silencing in tumor by controlling intracellular trafficking (2010)
  • Author(s): Hatakeyama H, et al.
  • Organizer: The 13th Annual Meeting of the American Society of Gene and Cell Therapy
  • Place of Presentation: Marriott Wardman Park Hotel, Washington DC, USA
  • Year and Date: 2010-05-20
• [Presentation] Application of siRNA-containing nanoparticles for in vitro and in vivo gene silencing in tumor by controlling intracellular trafficking (2010)
  • Author(s): Hatakeyama H, et al.
  • Organizer: The 13th Annual Meeting of the American Society of Gene and Cell Therapy
  • Place of Presentation: University of British Columbia, Vancouver, Canada.
  • Year and Date: 2010-05-20
• [Presentation] がんへの核酸デリバリーシステムの開発～PEGのジレンマへの挑戦～ (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 薬剤学会第25年会
  • Place of Presentation: 徳島県郷土文化会館(徳島)
  • Year and Date: 2010-05-12
• [Presentation] がんへの核酸デリバリーシステムの開発～PEGのジレンマへの挑戦～ (2010)
  • Author(s): 畠山浩人、秋田英万、原島秀吉
  • Organizer: 薬剤学会第25年会
  • Place of Presentation: 徳島、徳島県郷上文化会館(招待講演)
  • Year and Date: 2010-05-12
• [Presentation] 多機能性エンベロープ型ナノ構造体によるsiRNAの送達制御 (2010)
  • Author(s): 原島秀吉、秋田英万、畠山浩人
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山国際会議場(富山)
• [Presentation] エンドソーム脱出素子を搭載したsiRNAデリバリーシステムの開発 (2010)
  • Author(s): 櫻井遊、畠山浩人、秋田英万、二木史朗、原島秀吉
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山国際会議場(富山)
• [Presentation] オルニチン/トリプトファン(Orn/Trp)アナログを用いたがん細胞への効率的なsiRNAデリバリー (2010)
  • Author(s): 佐藤悠介、畠山浩人、原島秀吉
  • Organizer: 第26回日本DDS学会
  • Place of Presentation: 大阪国際交流センター(大阪)
• [Book] Comprehensive Biomaterials (2011)
  • Author(s): Akita H, Hatakeyama H, Khalil IA, Yamada Y, Harashima H
  • Total Pages: 3750
  • Publisher: Elsevier
• [Book] 蛍光イメージング/MRIプローブの開発 (2011)
  • Author(s): 秋田英万、山田勇磨、中村孝司、畠山浩人、林泰弘、梶本和昭、原島秀吉
  • Total Pages: 196
  • Publisher: シーエムシー出版
• [Book] Delivery of Nucleic Acids and Gene Delivery (2011)
  • Author(s): Akita H, Hatakeyama H, et al.
  • Publisher: Elsevier