Systemic delivery system of siRNAfor cancertreatment

2012 Fiscal Year Final Research Report

• 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
• Keywords: ドラッグデリバリーシステム / small interfering RNA / がん治療

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 Pages: 20-27
  • DOI: 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: 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 Pages: 269-274
  • DOI: 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. Kato, H. Ando, K. Shiraishi, M. Yokoyama, N. Oku
  • Journal Title: Int. J. Pharm. Volume: 432 Pages: 75-79
  • DOI: 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 Pages: 296-301
  • DOI: DOI:10.1016/j.ijpharm.2012.09.016
  • Peer Reviewed
• [Journal Article] Amelioration of cerebral ischemia-reperfusion injurybased 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: J. Control. Release Volume: 160 Pages: 81-87
  • DOI: 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 Pages: 177-181
  • DOI: 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 Pages: 274-280
  • DOI: 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): M. Ogata, M. Yano, S. Umemura, T. Murata, EY. Park, Y. Kobayashi, T. Asai, N. Oku, N. Nakamura, I. Matsuo, T. Usui
  • Journal Title: Bioconjug. Chem. Volume: 23 Pages: 97-105
  • DOI: DOI:10.1021/bc200440e
  • 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 Pages: 429-435
  • DOI: DOI:10.1021/bc1004697
  • 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
• [Book] Drug carrier systems for anticancer agents. (2013)
  • Author(s): H. Koide, T. Asai, K. Shimizu, N. Oku
  • Total Pages: 153-170
  • 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
• [Remarks]
  • URL: http://w3pharm.u-shizuoka-ken.ac.jp/radiobio/mbc/Publication.html