高分子型ミセルを用いた脳腫瘍標的テーラーメイドドラッグデリバリーの開発

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24659584
• Research Institution: The University of Tokyo
• Principal Investigator: 三浦 裕 東京大学, 医学(系)研究科(研究院), 助教 (40557980)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ドラッグデリバリー / ナノ材料 / 脳腫瘍

Outline of Annual Research Achievements

本年度は新たに腫瘍血管の内皮細胞や脳腫瘍で過剰発現が認められるαVβ3およびαVβ5インテグリンに対して特異的に結合する環状RGDペプチド(cRGD)をリガンド分子として搭載したエピルビシン内包ミセルを開発した。具体的にはcRGDをポリエチレングリコール（PEG）の末端へ導入したPEG－ポリグルタミン酸を合成し、そのグルタミン酸側鎖に対してpH応答性の結合を介してエピルビシンを導入した。得られたブロックポリマーは水中に於いて自己組織化し、粒径が30nmの高分子ミセルとなることが確認された。また、同cRGD導入ミセルは、ヒトGlioblastoma U87MG細胞に対して有効な細胞毒性を示した。U87MG細胞を皮下移植したマウスを用いて腫瘍の増殖抑制試験を行った結果、cRGD導入ミセルは特段の副作用を示すことなく、腫瘍の成長を抑制することが確認された。さらに、同所移植モデルに対しても優れた抗がん活性を示すことが確認された。

Research Products

• [Journal Article] Bundled assembly of helical nanostructures in polymeric micelles loaded with platinum drugs enhancing therapeutic efficiency against pancreatic tumor (2014)
  • Author(s): Y. Mochida, H. Cabral, Y. Miura, F. Albertini, S. Fukushima, K. Osada, N. Nishiyama, K. Kataoka
  • Journal Title: ACS Nano Volume: 8 Pages: 6724-6738
  • DOI: DOI: 10.1021/nn500498t
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Selective intracellular delivery of proteasome inhibitors through pH-sensitive polymeric micelles directed to efficient antitumor therapy (2014)
  • Author(s): S. Quader, H. Cabral, Y. Mochida, T. Ishii, X. Liu, K. Toh, H. Kinoh, Y. Miura, N. Nishiyama, K. Kataoka
  • Journal Title: Journal of Controlled Release Volume: 188 Pages: 67-77
  • DOI: DOI: 10.1016/j.jconrel.2014.05.048
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation (2014)
  • Author(s): H. Wu, H. Cabral, K. Toh, P. Mi, Y.-C. Chen, Y. Matsumoto, N. Yamada, X. Liu, H. Kinoh, Y. Miura, M. R. Kano, H. Nishihara, N. Nishiyama, K. Kataoka
  • Journal Title: Journal of Controlled Release Volume: 189 Pages: 1-10
  • DOI: DOI: 10.1016/j.jconrel.2014.06.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Light-induced cytosolic activation of reduction-sensitive camptothecin-loaded polymeric micelles for spatiotemporally controlled in vivo chemotherapy (2014)
  • Author(s): H.-C. Yen, H. Cabral, P. Mi, K. Toh, Y. Matsumoto, X. Liu, H. Koori, A. Kim, K. Miyazaki, Y. Miura, N. Nishiyama, K. Kataoka
  • Journal Title: ACS Nano Volume: 8 Pages: 11591-11602
  • DOI: DOI: 10.1021/nn504836s
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors (2014)
  • Author(s): Y. Oe, R. J. Christie, M. Naito, S. A. Low, S. Fukushima, K. Toh, Y. Miura, Y. Matsumoto, N. Nishiyama, K. Miyata, K. Kataoka
  • Journal Title: Biomaterials Volume: 35 Pages: 7887-7895
  • DOI: DOI: 10.1016/j.biomaterials.2014.05.041
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer (2014)
  • Author(s): J. -Y. Ahn, Y. Miura, N. Yamada, T. Chida, X. Liu, A. Kim, R. Sato, R. Tsumura, Y. Koga, M. Yasunaga, N. Nishiyama, Y. Matsumura, H. Cabral, K. Kataoka
  • Journal Title: Biomaterials Volume: 39 Pages: 23-30
  • DOI: DOI: 10.1016/j.biomaterials.2014.10.069
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Polymeric micelles loaded with platinum anticancer drugs target preangiogenic micrometastatic niches associated with inflammation (2014)
  • Author(s): H. Wu, H. Cabral, K. Toh, P. Mi, Y. Matsumoto, J. -Y. Ahn, H. Kinoh, N. Nishiyama, Y. Miura, K. Kataoka
  • Organizer: The 10th International Polymer Conference IPC2014
  • Place of Presentation: International Congress Center, Tsukuba, Ibaraki
  • Year and Date: 2014-12-02 – 2014-12-05
• [Presentation] Systemic targeting of lymph node metastasis by controlled design of drug-loaded polymeric micelles (2014)
  • Author(s): J. Makino, H. Cabral, Y. Miura, Y. Matsumoto, H. Kinoh, N. Nishiyama, K. Kataoka
  • Organizer: 12th International Nanomedicine and Drug Delivery Symposium (NanoDDS'14)
  • Place of Presentation: UNC Eshelman School of Pharmacy and Duke University, North Carolina, USA
  • Year and Date: 2014-10-06 – 2014-10-08
• [Presentation] Development of a specific targeting system for pancreatic tumors utilizing antibody conjugated Pt-loaded micelles (2014)
  • Author(s): J. -Y. Ahn, N. Yamada, A. Kim, T. Chida, Y. Miura, H. Cabral, Y. Matsumura, N. Nishiyama, K. Kataoka
  • Organizer: 41st Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: The Hilton Chicago, Chicago, Illinois, USA
  • Year and Date: 2014-07-13 – 2014-07-16
• [Presentation] Development of a glutathione sensitive polymeric micelles for the delivery of campothecin to solid tumors (2014)
  • Author(s): H.-C. Yen, H. Cabral, H. Koori, Y. Miura, P. Mi, A. Kim, N. Nishiyama, K. Kataoka
  • Organizer: 41st Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: The Hilton Chicago, Chicago, Illinois, USA
  • Year and Date: 2014-07-13 – 2014-07-16
• [Presentation] Efficient intracellular delivery of monoclonal antibodies into the living cells by charge-conversional polyionic complex micelles (2014)
  • Author(s): A. Kim, Y. Miura, T. Ishii, K. Kataoka
  • Organizer: 41st Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: The Hilton Chicago, Chicago, Illinois, USA
  • Year and Date: 2014-07-13 – 2014-07-16
• [Presentation] Ligand-linked polymeric micelles for targeted delivery of platinum anti-cancer drug into malignant tumor (2014)
  • Author(s): Y. Miura, K. Kataoka
  • Organizer: The Drug Discovery & Therapy World Congress 2014
  • Place of Presentation: John B. Hynes Veterans Mmemorial Convention Center, Boston, Massachusetts, USA
  • Year and Date: 2014-06-16 – 2014-06-19
  • Invited
• [Book] The Frontiers in Life Sciencesシリーズ 生命科学から創薬へのイノベーション 第18章 ドラッグデリバリー (2014)
  • Author(s): 三浦裕、片岡一則
  • Total Pages: 8
  • Publisher: 南山堂
• [Remarks] 東京大学片岡研究室
  • URL: http://www.bmw.t.u-tokyo.ac.jp/