Development of efficient drug and gene delivery system for malignant brain tumors using polymeric nanomicelles.

• Project/Area Number: 24390340
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: INO Yasushi 東京大学, 医科学研究所, 准教授 (50372371)
• Co-Investigator(Kenkyū-buntansha): KATAOKA Kazunori 東京大学, 大学院工学系研究科, 教授 (00130245)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Nobuhiro 東京工業大学, 資源化学研究所, 教授 (10372385) ; TODO Tomoki 東京大学, 医科学研究所, 教授 (80272566)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: 悪性脳腫瘍 / ドラッグ・デリバリー / 脳腫瘍 / ドラッグデリバリー / 脳腫瘍学 / 癌 / 脳神経腫瘍 / ナノ材料 / 生体材料

Outline of Final Research Achievements

We performed a basic research on the method to enhance the efficacy of polymeric nanomicelles as a drug and gene delivery system. The polymeric nanomicelles consist of block polymers which were designed to achieve selective and efficient accumulation to solid tumors including brain tumors. In order to use the polymeric nanomicelles in combination with oncolytic HSV-1 virus therapy, several in vivo mice tumor models were studied, mainly using marker gene expressing HSV-1. When RGD peptide was used as a ligand to αvβ3 and αvβ5 integrins, the functional micelle showed improved accumulation to αvβ3 and αvβ5 integrin expressing tumor tissue and enhanced antitumor effect in vivo

Research Products

• [Journal Article] 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex (2014)
  • Author(s): Hiroki Takai, Tetsu Akiyama et al.
  • Journal Title: Cell Reports Volume: 9 Issue: 1 Pages: 48-60
  • DOI: 10.1016/j.celrep.2014.08.071
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier (2013)
  • Author(s): Y. Miura, N. Nishiyama, et al.
  • Journal Title: ACS Nano Volume: 7 Issue: 10 Pages: 8583-8592
  • DOI: 10.1021/nn402662d
  • Peer Reviewed
• [Journal Article] An armed oncolytic herpes simplex virus expressing thrombospondin-1 has an enhanced in vivo antitumor effect against human gastric cancer. (2013)
  • Author(s): Tsuji T, Nakamori M, et al.
  • Journal Title: Int J Cancer Volume: 132 Issue: 2 Pages: 485-494
  • DOI: 10.1002/ijc.27681
  • Peer Reviewed
• [Journal Article] The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. (2012)
  • Author(s): Koyama-Nasu R, Nasu-Nishimura Y, Todo T, Ino Y, Saito N, Aburatani H, Funato K, Echizen K, Sugano H, Haruta R, Matsui M, Takahashi R, Manabe E,
  • Journal Title: Oncogene
  • Peer Reviewed
• [Presentation] Generation of a therapeutic antibody-expressing oncolytic herpes simplex virus. (2014)
  • Author(s): 伊藤博崇、稲生靖、田中実、藤堂具紀
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] がん治療用ウイルス(G47Δ)とマイクロRNA阻害を併用した悪性グリオーマ治療の開発 (2013)
  • Author(s): 伊藤 元一、稲生 靖、田中 実、伊藤 博崇、藤堂 具紀
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: 宮崎
• [Presentation] 悪性脳腫瘍に対するウイルス療法の研究開発 (2012)
  • Author(s): 稲生靖
  • Organizer: 台癌のトランスレーショナル研究シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2012-11-21
• [Presentation] Oncolytic HSV-1 virus therapy targeti ng glioblastoma-derived cancer stem cells (2012)
  • Author(s): Ino Y, Fukuhara H, Takahashi M, Nakatsubo T, Todo T
  • Organizer: The 19th Tnternatlonal Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Niagara Falls, Canada