Systemic delivery system of siRNAfor cancertreatment

• Project/Area Number: 22790045
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: ASAI Tomohiro 静岡県立大学, 大学院・薬学研究科, 准教授 (00381731)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ドラッグデリバリーシステム / small interfering RNA / がん治療 / ＲＮＡ干渉 / ｓｉＲＮＡ / がん / ＤＤＳ / リポソーム / RNA干渉 / siRNA / DDS

Research Abstract

RNA interference effectorssuch assmall interfering RNA (siRNA) are promising therapeutic tools for treating cancer.Apractical and applicable delivery system is required to deliver enough of the therapeutic RNA to target tissues.In this study, we developed novel lipid nanoparticles carrying cholesterol-grafted siRNA for RNAi-based cancer therapy. Inhibitionof mammalian target of rapamycin(mTOR) signaling with siRNA systemically deliveredby thelipid nanoparticles resulted in tumor suppressionin vivo.

Research Products

• [Journal Article] Development of miR-92a delivery system for antiangiogenesis-based cancer therapy. (2013)
  • Author(s): H. Ando, A. Okamoto, M. Yokota, K. Shimizu, T. Asai, T. Dewa, N. Oku
  • Journal Title: J. Gene Med. Volume: 15 Issue: 1 Pages: 20-27
  • DOI: 10.1002/jgm.2690
  • Peer Reviewed
• [Journal Article] Liposomes and nanotechnology in drug development: focus on ocular targets. (2013)
  • Author(s): M. Honda, T. Asai, N. Oku, Y. Araki, M. Tanaka, N. Ebihara
  • Journal Title: Int J Nanomedicine Volume: 8 Pages: 495-504
  • DOI: 10.2147/ijn.s30725
  • Peer Reviewed
• [Journal Article] A single injection of liposomal asialo-erythropoietin improves motor function deficit caused by cerebral ischemia/reperfusion. (2012)
  • Author(s): T. Ishii, T. Asai, T. Fukuta, D. Oyama, N. Yasuda, Y. Agato, K. Shimizu, T. Minamino, N. Oku
  • Journal Title: Int. J. Pharm. Volume: 439 Issue: 1-2 Pages: 269-274
  • DOI: 10.1016/j.ijpharm.2012.09.026
  • Peer Reviewed
• [Journal Article] Size-dependent induction of accelerated blood clearance phenomenon by repeated injections of polymeric micelles (2012)
  • Author(s): H. Koide, T. Asai, H. Ando, K. Shiraishi,M. Yokoyama, and N. Oku
  • Journal Title: International Journal of Pharmaceutics Volume: 432 Issue: 1-2 Pages: 75-79
  • DOI: 10.1016/j.ijpharm.2012.04.049
  • Peer Reviewed
• [Journal Article] Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets. (2012)
  • Author(s): K. Tokutomi, T. Tagawa, M. Korenaga, M. Chiba, T. Asai, N. Watanabe, S. Takeoka, M. Handa, Y. Ikeda, N. Oku
  • Journal Title: Int J Pharm. Volume: 438 Issue: 1-2 Pages: 296-301
  • DOI: 10.1016/j.ijpharm.2012.09.016
  • Peer Reviewed
• [Journal Article] Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin (2012)
  • Author(s): T.Ishii, T.Asai, D.Oyama, T.Fukuta, N.Yasuda, K.Shimizu, T.Minamino, N.Oku
  • Journal Title: Journal of Controlled Release Volume: (In press) Issue: 1 Pages: 81-87
  • DOI: 10.1016/j.jconrel.2012.02.004
  • Peer Reviewed
• [Journal Article] RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment. (2012)
  • Author(s): Yonenaga N, Kenjo E, Asai T,Tsuruta A, Shimizu K, Dewa T, Nango M, Oku N:
  • Journal Title: J. Control. Release Volume: 160 Issue: 2 Pages: 177-181
  • DOI: 10.1016/j.jconrel.2011.10.004
  • Peer Reviewed
• [Journal Article] Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer. (2012)
  • Author(s): K. Nishikawa, T. Asai, H. Shigematsu, K. Shimizu, H. Kato, Y. Asano, S. Takashima, E. Mekada, N. Oku, T. Minamino
  • Journal Title: J. Control. Release Volume: 160 Issue: 2 Pages: 274-280
  • DOI: 10.1016/j.jconrel.2011.10.010
  • Peer Reviewed
• [Journal Article] Design and synthesis of high-avidity tetravalent glycoclusters as probes for Sambucus sieboldiana agglutinin and characterization of their binding properties (2012)
  • Author(s): Ogata, M., Yano, M., Umemura, S., Murata, T., Park, E.Y., Kobayashi, Y., Asai, T., Oku, N., Nakamura, N., Matsuo, I., Usui, T.
  • Journal Title: Bioconjugate Chem. Volume: 23 Issue: 1 Pages: 97-105
  • DOI: 10.1021/bc200440e
  • Peer Reviewed
• [Journal Article] Nanoparticle-mediated delivery of anticancer agents to tumor angiogenic vessels. (2012)
  • Author(s): Asai T
  • Journal Title: Biol. Pharm. Bull. Volume: 35 Pages: 1855-1861
  • NAID: 130001872277
  • Peer Reviewed
• [Journal Article] siRNAデリバリーシステムのPET解析と核酸医薬品開発への応用 (2012)
  • Author(s): 浅井知浩
  • Journal Title: YAKUGAKU ZASSHI Volume: 132 Pages: 1159-1163
  • Peer Reviewed
• [Journal Article] Dicetyl phosphate-tetraethylenepentamine-based liposomes for systemic siRNA delivery. (2011)
  • Author(s): T. Asai, S. Matsushita, E. Kenjo, T. Tsuzuku, N. Yonenaga, H. Koide, K. Hatanaka, T. Dewa, M. Nango, N. Maeda, H. Kikuchi, N. Oku
  • Journal Title: Bioconjug. Chem. Volume: 22 Issue: 3 Pages: 429-435
  • DOI: 10.1021/bc1004697
  • Peer Reviewed
• [Journal Article] Inhibition of Akt (ser473) phosphorylation and rapamycin-resistant cell growth by knockdown of mammalian target of rapamycin with siRNA in VEGFR-1-targeting vector (2011)
  • Author(s): Koide, H., et al.
  • Journal Title: Biol.Pharm.Bull. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Proapoptotic action of p53-Tom5 in p53-resistant A549 human non-small cell lung cancer cells through direct mitochondrial dysfunction (2011)
  • Author(s): Umemoto, T., et al.
  • Journal Title: Biol.Pharm.Bull. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Dicetyl phosphate -tetraethylenepentamine -based liposomes for systemic siRNA delivery (2011)
  • Author(s): Asai, T., et al.
  • Journal Title: Bioconjug.Chem. Volume: 22 Pages: 429-435
  • Peer Reviewed
• [Journal Article] Suppression of choroidal neovascularization by intravitreal injection of liposomal SU5416 (2011)
  • Author(s): Honda, M., et al.
  • Journal Title: Arch.Ophthalmol. Volume: 129 Pages: 317-321
  • Peer Reviewed
• [Journal Article] Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets (2011)
  • Author(s): Tokutomi, K., et al.
  • Journal Title: Int.J.Pharm. Volume: 407 Pages: 151-157
  • Peer Reviewed
• [Journal Article] PET imaging of brain cancer with positron emitter-labeled liposomes (2011)
  • Author(s): Oku, N., et al.
  • Journal Title: Int.J.Pharm. Volume: 403 Pages: 170-177
  • Peer Reviewed
• [Journal Article] Anti-obesity effect of phosphatidylinositol on diet-induced obesity in mice (2010)
  • Author(s): Shimizu, K., et al.
  • Journal Title: J.Agric.Food Chem. Volume: 58 Pages: 11218-11225
  • Peer Reviewed
• [Journal Article] Liposomal polyamine-dialkyl phosphate conjugates as effective gene carriers : chemical structure, morphology, and gene transfer activity (2010)
  • Author(s): Dewa, T., et al.
  • Journal Title: Bioconjug.Chem. Volume: 21 Pages: 844-852
  • Peer Reviewed
• [Presentation] 脂質ナノ粒子を用いた腫瘍新生血管への核酸・薬物デリバリー (2013)
  • Author(s): 浅井知浩
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-30
• [Presentation] 脂質ナノ粒子を用いたsmall RNAデリバリー (2012)
  • Author(s): 浅井知浩、奥直人
  • Organizer: 創剤カンファレンス静岡
  • Place of Presentation: 静岡
  • Year and Date: 2012-12-14
• [Presentation] Targeted delivery of small interfering RNA with RGD-decorated polycation liposomes for cancer therapy. (2012)
  • Author(s): Tomohiro Asai, Naoto Oku
  • Organizer: Oligonucleotide Delivery: Biology, Engineering and Development
  • Place of Presentation: Hernstein, Austria
  • Year and Date: 2012-10-09
• [Presentation] siRNAイメージング技術の開発とデリバリーシステム研究への応用 (2012)
  • Author(s): 浅井知浩
  • Organizer: 第58回日本薬学会東海支部総会・大会
  • Place of Presentation: 静岡
  • Year and Date: 2012-07-07
• [Presentation] Active targeting DDS for cancer RNAi therapy (2011)
  • Author(s): Naoto Oku, et al
  • Organizer: The 4^<th> International Conference on Health and Longevity Sciences
  • Place of Presentation: 静岡
  • Year and Date: 2011-10-21
• [Presentation] In vivo imaging of liposomal siRNA delivery by positron emission tomography (2011)
  • Author(s): Hidenori Ando, et al
  • Organizer: The 4^<th> International Conference on Health and Longevity Sciences
  • Place of Presentation: 静岡
  • Year and Date: 2011-10-21
• [Presentation] mTORを標的とした腫瘍RNA干渉療法の開発 (2011)
  • Author(s): 加藤寛己, ら
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-29
• [Presentation] Anti-cancer RNA interference therapy targeting to mammalian target of rapamycin (2011)
  • Author(s): Hiroki Kato, et al
  • Organizer: Liposomes in Jerusalem 2011
  • Place of Presentation: Jerusalem, Israel
  • Year and Date: 2011-05-15
• [Presentation] Treatment of gynecological cancer with anti-HB-EGF antibody-modified liposomes encapsulating doxorubicin (2011)
  • Author(s): Kaoru Nishikawa, et al
  • Organizer: Liposomes in Jerusalem 2011
  • Place of Presentation: Jerusalem, Israel
  • Year and Date: 2011-05-15
• [Presentation] Systemic siRNA delivery system using novel polycation liposomes for cancer treatment (2011)
  • Author(s): Norihito Yonenaga, et al
  • Organizer: Liposomes in Jerusalem 2011
  • Place of Presentation: Jerusalem, Israel
  • Year and Date: 2011-05-15
• [Presentation] リポソームDDSによる腫瘍新生血管傷害療法 (2011)
  • Author(s): 浅井知浩
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-29
• [Presentation] ポジトロン標識siRNAによるDDS研究への応用 (2010)
  • Author(s): 畑中剣太朗, ら
  • Organizer: 第10回放射医薬品・画像診断薬研究会
  • Place of Presentation: 京都
  • Year and Date: 2010-12-04
• [Presentation] リポソームを用いた全身投与型siRNAデリバリーシステムの開発 (2010)
  • Author(s): 浅井知浩
  • Organizer: 第28回製剤設計研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-23
• [Presentation] 遺伝子送達能を有するポリアミン脂質の開発とその機能評価:原子間力顕微鏡によるDNA複合体の形態観察とその作用機構 (2010)
  • Author(s): 加藤清志, ら
  • Organizer: 第19回DDSカンファランス
  • Place of Presentation: 静岡
  • Year and Date: 2010-09-04
• [Presentation] Pharmacokinetic PET studies of liposomal siRNA (2010)
  • Author(s): Tomohiro Asai, et al.
  • Organizer: LRD/LLMB 2010 Conference
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-04
• [Presentation] Liposomal polyamine-dialkyl phosphate conjugates as effective gene carriers : Chemical structure, morphology, and gene transfer activity (2010)
  • Author(s): Takehisa Dewa, et al.
  • Organizer: LRD/LLMB 2010 Conference
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-04
• [Presentation] Development of in vivo delivery system for siRNA-based cancer therapy (2010)
  • Author(s): Takuma Tsuzuku, et al.
  • Organizer: LRD/LLMB 2010 Conference
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-04
• [Presentation] RNA創薬に向けたsiRNA体内動態のPETイメージング (2010)
  • Author(s): 浅井知浩, ら
  • Organizer: 第56回日本薬学会東海支部総会・大会
  • Place of Presentation: 岐阜
  • Year and Date: 2010-07-03
• [Presentation] 新規PCLを用いた全身投与型siRNAデリバリーシステムのがん治療への応用 (2010)
  • Author(s): 米永憲史, ら
  • Organizer: 第26回DDS学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-06-17
• [Presentation] mTORを標的とした腫瘍新生血管障害療法の開発 (2010)
  • Author(s): 小出裕之, ら
  • Organizer: 日本薬剤学会第25年会
  • Place of Presentation: 徳島
  • Year and Date: 2010-05-12
• [Presentation] RNA創薬研究におけるポジトロン標識siRNAのPET体内動態イメージング (2010)
  • Author(s): 畑中剣太朗, ら
  • Organizer: 日本薬剤学会第25年会
  • Place of Presentation: 徳島
  • Year and Date: 2010-05-12
• [Presentation] ポリカチオニックリポソームを用いたmicroRNA送達への応用
  • Author(s): 安藤英紀ら
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
• [Presentation] ポリカチオンリポソームを用いたmiR-92aの細胞内送達と抗血管新生効果の検討
  • Author(s): 安藤英紀ら
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌
• [Presentation] siRNAイメージング技術の開発とデリバリーシステム研究への応用
  • Author(s): 浅井知浩
  • Organizer: 第58回日本薬学会東海支部総会･大会
  • Place of Presentation: 静岡
  • Invited
• [Presentation] 抗体修飾脂質ナノ粒子を用いた核酸送達技術の開発
  • Author(s): 岡本彩香ら
  • Organizer: 第58回日本薬学会東海支部総会･大会
  • Place of Presentation: 静岡
• [Presentation] 抗体修飾脂質ナノ粒子を用いたsiRNAデリバリー技術の開発
  • Author(s): 岡本彩香ら
  • Organizer: アンチセンス・遺伝子・デリバリーシンポジウム2012
  • Place of Presentation: 仙台
• [Presentation] Antiangiogenic Therapy by delivery of MIR-92A to angiogenic endothelial cells
  • Author(s): Hidenori Ando et al
  • Organizer: Oligonucleotide Delivery
  • Place of Presentation: Hernstein, Austria
• [Presentation] Targeted delivery of small interfering RNA with RGD-decorated polycation liposomes for cancer therapy
  • Author(s): Tomohiro Asai et al
  • Organizer: Oligonucleotide Delivery
  • Place of Presentation: Hernstein, Austria
  • Invited
• [Presentation] Antiangiogenic RNAi therapy
  • Author(s): Naoto Oku et al
  • Organizer: Liposome Research Days 2012
  • Place of Presentation: Hangzhou, China
  • Invited
• [Presentation] プロタミン由来膜透過ペプチドを提示した脂質ナノ粒子によるsiRNAデリバリー
  • Author(s): 高橋翔弥ら
  • Organizer: 第34回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 京都
• [Presentation] miR-92aの細胞内送達と抗血管新生療法への応用
  • Author(s): 安藤英紀ら
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] がん細胞へのsiRNA送達を目指した機能性ナノキャリアの開発
  • Author(s): 岡本彩香ら
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 脂質ナノ粒子を用いたsmall RNAデリバリー
  • Author(s): 浅井知浩ら
  • Organizer: 創剤カンファレンス静岡
  • Place of Presentation: 静岡
  • Invited
• [Presentation] 脂質ナノ粒子を用いた腫瘍新生血管への核酸・薬物デリバリー
  • Author(s): 浅井知浩ら
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Invited
• [Book] Drug carrier systems for anticancer agents. (2013)
  • Author(s): H. Koide, T. Asai, K. Shimizu, N. Oku
  • Publisher: CRC Press
• [Book] Polymeric Biomaterials (2013)
  • Author(s): Koide H et al
  • Total Pages: 18
  • Publisher: CRC Press
• [Book] Polyamine-lipid conjugates as effective gene carriers: chemical structure, morphology, and gene transfer activity. (2011)
  • Author(s): T. Dewa, T. Asai, N. Oku, M. Nango
  • Publisher: In Tech
• [Book] Non-Viral Gene Therapy (2011)
  • Author(s): Takehisa Dewa, et al
  • Total Pages: 23
  • Publisher: In Tech
• [Remarks]
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/radiobio/mbc/Publication.html
• [Remarks] Publications & Awards
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/radiobio/mbc/Publication.html