Development of cancer-controlling vector conversion techniques using nano-DDS

• Project Area: Conversion of tumor-regulation vector to intercept oncogenic spiral accelerated by infection and inflammation
• Project/Area Number: 22114009
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: AKIYOSHI Kazunari 京都大学, 工学(系)研究科(研究院), 教授 (90201285)
• Co-Investigator(Kenkyū-buntansha): SHINYA Masaharu 京都府立医科大学, 医学部, 研究員 (10405277) ; MATSUDA Osamu 京都府立医科大学, 医学研究科, 教授 (00271164) ; 澤田 晋一 京都大学, 工学研究科, 助教 (50444104) ; 佐々木 善浩 東京医科歯科大学, 生体材料工学研究所, 准教授 (90314541)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥138,060,000 (Direct Cost: ¥106,200,000、Indirect Cost: ¥31,860,000); Fiscal Year 2014: ¥25,870,000 (Direct Cost: ¥19,900,000、Indirect Cost: ¥5,970,000); Fiscal Year 2013: ¥27,040,000 (Direct Cost: ¥20,800,000、Indirect Cost: ¥6,240,000); Fiscal Year 2012: ¥28,340,000 (Direct Cost: ¥21,800,000、Indirect Cost: ¥6,540,000); Fiscal Year 2011: ¥28,080,000 (Direct Cost: ¥21,600,000、Indirect Cost: ¥6,480,000); Fiscal Year 2010: ¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000)
• Keywords: ドラッグデリバリーシステム / がん治療 / ナノゲル / ワクチン / エクソソーム / siRNA / 腫瘍微小環境 / 細胞特異性 / RGDペプチド / 抗体 / サイトカイン / タンパク質デリバリー / 核酸デリバリー / エンドサイトーシス / 遺伝子導入 / シャペロン機能

Outline of Final Research Achievements

The aim of this research project is to invent new technologies to fully control the delivery, expression, and sustained release of bioactive molecules, such as DNA, siRNA, and proteins, by further modifying existing nanogel DDSs. We newly developed polysaccharide-nanogels for nucleic acids (CpG, siRNA) delivery systems. We succeeded to control cancer microenvironments and to reduce the growth of cancers by using nanogel-siRNA delivery system.

Research Products

• [Journal Article] Effective CpG DNA delivery using amphiphilic cycloamylose nanogels (2015)
  • Author(s): Y. Tahara, J. Yasuoka, S. Sawada, Y. Sasaki, K. Akiyoshi
  • Journal Title: Biomaterials Science Volume: 3 Issue: 2 Pages: 256-264
  • DOI: 10.1039/c4bm00293h
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A Nanogel-based Immunologically Stealth Vaccine Targets Macrophages in the Medulla of Lymph Node and Induces Potent Anti-Tumor Immunity (2014)
  • Author(s): D. Muraoka, N. Harada, T. Hayashi, Y. Tahara, F. Momose, S. Sawada, S. Mukai, K. Akiyoshi, H. Shiku,
  • Journal Title: ACS nano Volume: 8 Issue: 9 Pages: 9209-9218
  • DOI: 10.1021/nn502975r
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Therapeutic Effect of Nanogel-Based Delivery of Soluble FGFR2 with S252W Mutation on Craniosynostosis (2014)
  • Author(s): M. Yokota, Y. Kobayashi, J. Morita, H. Suzuki, Y. Hashimoto, Y. Sasaki, K. Akiyoshi, K. Moriyama
  • Journal Title: PLOS ONE Volume: 9 Issue: 7 Pages: e101693-e101693
  • DOI: 10.1371/journal.pone.0101693
  • Peer Reviewed / Open Access
• [Journal Article] Cycloamylose-Nanogel DDS-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment (2014)
  • Author(s): H. Fujii, M. Shin-Ya, S. Takeda, Y. Hashimoto, S. Mukai, S. Sawada, T. Adachi, K. Akiyoshi, T. Miki, O. Mazda
  • Journal Title: Cancer Science Volume: 105 Issue: 12 Pages: 1616-1625
  • DOI: 10.1111/cas.12547
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microrheology of nanogel-integrated system, (2014)
  • Author(s): Y. Sekine, K. Okazaki, T. Ikeda-Fukazawa, M. Ichikawa, K. Yoshikawa, S. Mukai, K. Akiyoshi,
  • Journal Title: Colloid Polym. Sci., Volume: 292 Pages: 325-331
  • Peer Reviewed
• [Journal Article] Polysaccharide-hair cationic polypeptide nanogels: Self-assembly and enzymatic polymerization of amylose primer modified cholesteryl poly(L-lysine) (2013)
  • Author(s): N. Morimoto, M. Yamazaki, J. Tamada, K. Akiyoshi,
  • Journal Title: Langmuir Volume: 29 Pages: 7509-7514
  • Peer Reviewed
• [Journal Article] Cationic amphiphilic polysaccharide nanoballs: protein stabilization and intracellular delivery by nanoencapsulation (2013)
  • Author(s): H. Takahashi, S. Sawada, K. Akiyoshi,
  • Journal Title: Biomaterials Science Volume: 1 Pages: 842-849
  • Peer Reviewed
• [Journal Article] Cyclodextrin triggered dimensional changes of polysaccharide nanogel integrated hydrogels at nanometer resolution, (2013)
  • Author(s): M. Gao, S. Toita, S. Sawada, K. Akiyoshi, B. T. Stokke,
  • Journal Title: Soft matter Volume: 9 Pages: 5178-5185
  • Peer Reviewed
• [Journal Article] Self-Assembled pH-Sensitive Cholesteryl Pullulan Nanogel As a Protein Delivery Vehicle (2013)
  • Author(s): Nobuyuki Morimoto, Sayaka Hirano, Haruko Takahashi, Scott Loethen, David H. Thompson, Kazunari Akiyoshi
  • Journal Title: Biomacromolecules Volume: 14 Issue: 1 Pages: 56-63
  • DOI: 10.1021/bm301286h
  • Peer Reviewed
• [Journal Article] A Hybrid Hydrogel BIomaterial by Nanogel Engineering: Bottom-Up Design with Nanogel and Liposome Building Blocks to Develop a Multidrug Delivery System (2012)
  • Author(s): Y. Sekine, Y. Moritani, T. Ikeda-Fukazawa, Y. Sasaki, K. Akiyoshi
  • Journal Title: Advanced Healthcare Mater Volume: 1 Issue: 6 Pages: 722-728
  • DOI: 10.1002/adhm.201200175
  • Peer Reviewed
• [Journal Article] Injectable Hydrogel for Sustained Protein Release by Salt-Induced Association of Hyaluronic Acid Nanogel (2012)
  • Author(s): T. Nakai, et al
  • Journal Title: Macromolecular bioscience Volume: 12 Issue: 4 Pages: 475-483
  • DOI: 10.1002/mabi.201100352
  • Peer Reviewed
• [Journal Article] Dual crosslinked hydrogel nanoparticles by nanogel bottom-up method for sustained-release delivery (2011)
  • Author(s): Asako Shimoda, et al
  • Journal Title: Colloids Surf B Biointerfaces Volume: (in press) Pages: 38-44
  • DOI: 10.1016/j.colsurfb.2011.09.025
  • Peer Reviewed
• [Journal Article] Exploitation of a novel polysaccharide nanogel cross-linking membrane for guided bone regeneration (GBR) (2011)
  • Author(s): Takayuki Miyahara, et al
  • Journal Title: J Tissue Eng Regen Med Volume: (in press) Issue: 8 Pages: 666-672
  • DOI: 10.1002/term.475
  • Peer Reviewed
• [Journal Article] Nanogel-Based Scaffold Delivery of Prostaglandin E2 Receptor-Specific Agonist in Combination With a Low Dose of Growth Factor Heals Critical-Size Bone Defects in Mice (2011)
  • Author(s): P.Kamolratanakul, et al
  • Journal Title: Arthritis and Rheumatism Volume: 63 Issue: 4 Pages: 1021-1033
  • DOI: 10.1002/art.30151
  • Peer Reviewed
• [Journal Article] Cell specific peptide-conjugated polysaccharide nanogels for protein delivery (2011)
  • Author(s): Asako Shimoda, et al
  • Journal Title: Macromol Biosci Volume: Vol.11 Issue: 7 Pages: 882-888
  • DOI: 10.1002/mabi.201000491
  • Peer Reviewed
• [Journal Article] Cationic nanogels efficiently deliver proteins to myeloma cells and primary T lymphocytes poorly expressing heparan sulfate (2011)
  • Author(s): K.Watanabe, et al
  • Journal Title: Biomaterials Volume: 32 Issue: 25 Pages: 5900-5905
  • DOI: 10.1016/j.biomaterials.2011.04.058
  • Peer Reviewed
• [Journal Article] Polysaccharide nanogel gene delivery system with endosome-escaping function: Co-delivery of plasmid DNA and phospholipase A2 (2011)
  • Author(s): Toita S, Sawada S, Akiyoshi K
  • Journal Title: J Controlled Release Volume: 155 Issue: 1 Pages: 54-59
  • DOI: 10.1016/j.jconrel.2010.12.008
  • Peer Reviewed
• [Journal Article] The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae (2011)
  • Author(s): K.Nagano, N.Alles, A.H.Mian, A.Shimoda, N.Morimoto, Y.Tamura, H.Shimokawa, K.Akiyoshi, K.Ohya, K.Aoki
  • Journal Title: J Bone Miner, Metab Volume: 29 Issue: 6 Pages: 671-681
  • DOI: 10.1007/s00774-011-0270-z
  • Peer Reviewed
• [Journal Article] Amphiphilic polysaccharide nanoballs : a new building block for nanogel biomedical engineering and artificial chaperone (2011)
  • Author(s): H.Takahashi, et al
  • Journal Title: ACS Nano Volume: 5 Pages: 337-345
  • Peer Reviewed
• [Journal Article] Development of an Artificial Chaperone System Based on Cyclodextrin (2010)
  • Author(s): Y.Sasaki, et al
  • Journal Title: Current Pharmaceutical Biotechnology Volume: 11 Pages: 300-305
  • Peer Reviewed
• [Journal Article] Nanogel antigenic protein delivery system for adjuvant-free intranasal vaccines (2010)
  • Author(s): T.Nochi, et al
  • Journal Title: Nature Materials Volume: 9 Pages: 572-578
  • Peer Reviewed
• [Journal Article] Polysaccharide nanogel-cyclodextrin system as artificial chaperone for in vitro protein synthesis of green fluorescent protein (2010)
  • Author(s): Y.Sasaki, et al
  • Journal Title: Polymer Journal Volume: 42 Pages: 823-828
  • NAID: 10026687316
  • Peer Reviewed
• [Presentation] ナノゲル工学の提唱と新規DDSの開発 (2014)
  • Author(s): 秋吉一成
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 慶応義塾大学芝共立キャンパス(東京都港区）
  • Year and Date: 2014-07-31
  • Invited
• [Presentation] Bio-inspired Nanogel Engineering for Protein DDS (2014)
  • Author(s): Kazunari Akiyoshi
  • Organizer: 2014 IUPAC World Polymer Cogress or MACRO 2014
  • Place of Presentation: Chiang Mai province (Thailand)
  • Year and Date: 2014-07-06
  • Invited
• [Presentation] Self-Assembled Nanogel Engineering for DDS (2014)
  • Author(s): Kazunari Akiyoshi
  • Organizer: The 5th International Conference on the Development of Biomedical Engineering
  • Place of Presentation: Ho Chi Minh City (Vietnam)
  • Year and Date: 2014-06-17
  • Invited
• [Presentation] ナノゲル工学による新規DDSの開発 (2014)
  • Author(s): 秋吉一成
  • Organizer: BIO tech 2014（第13回国際バイオテクノロジー展/技術会議）
  • Place of Presentation: 東京ビックサイト(東京都江東区）
  • Year and Date: 2014-05-15
  • Invited
• [Presentation] 糖ナノゲルテクトニクスによる新規バイオ材料の設計と医療応用 (2013)
  • Author(s): 秋吉一成
  • Organizer: 第63回医用高分子研究会 主題＝ 実用化・臨床化のための医用高分子研究
  • Place of Presentation: 東京医科歯科大学（東京都）
  • Year and Date: 2013-03-13
  • Invited
• [Presentation] ナノゲルDDSによる発がんスパイラル制御 (2013)
  • Author(s): 秋吉一成
  • Organizer: 平成24年度 文部科学省新学術領域研究（研究代表者 今井浩三）「がん研究分野の特性等を踏まえた支援活動」公開シンポジウム
  • Place of Presentation: 学術総合センター，一橋記念講堂（東京都）
  • Year and Date: 2013-01-29
  • Invited
• [Presentation] Self-assembled nanogel engineering by associating polymers (2012)
  • Author(s): K. Akiyoshi
  • Organizer: IACIS (International Association of Colloid and Interface Scientists) Conference
  • Place of Presentation: 仙台国際会議場（宮城県）
  • Year and Date: 2012-05-17
  • Invited
• [Presentation] ナノゲルドラッグデリバリーシステムと免疫 (2012)
  • Author(s): 秋吉一成
  • Organizer: 第31回岡山免疫懇話会
  • Place of Presentation: 岡山大学病院(招待講演)
  • Year and Date: 2012-03-07
• [Presentation] ナノゲル工学による先端医療への展開 (2011)
  • Author(s): 秋吉一成
  • Organizer: 第21回高分子ゲル研究会講座高分子ゲルの応用展開～実用化に向けた応用研究の最前線～
  • Place of Presentation: 東京理科大学(招待講演)
  • Year and Date: 2011-11-18
• [Presentation] 多糖ナノゲル工学による新規DDS設計 (2011)
  • Author(s): 秋吉一成
  • Organizer: 第27回日本DDS学会企業セミナー
  • Place of Presentation: 東京大学(招待講演)
  • Year and Date: 2011-06-09
• [Presentation] Polysaccharide Nanogels for Immunotherapy (2011)
  • Author(s): K.Akiyoshi
  • Organizer: The 10th China-Japan-Korea Foresight Joint Symposium on Gene Delivery and International Symposium on Biomaterials 2011
  • Place of Presentation: Guilin, Guangxi, China(招待講演)
  • Year and Date: 2011-05-30
• [Presentation] ナノゲル工学による新規DDSの開発 (2011)
  • Author(s): 秋吉一成
  • Organizer: 日本膜学会第33年会境界領域シンポジウム「ナノ粒子表面物性に基づいたDDS開発」
  • Place of Presentation: 産業技術総合研究所(東京都)(招待講演)
  • Year and Date: 2011-05-13
• [Presentation] Polysaccharide nanogel protein delivery system for immunotherapy (2011)
  • Author(s): K.Akiyoshi
  • Organizer: Ninth International Symposium on Frontiers in Biomedical Polymers FBPS 2011
  • Place of Presentation: Funchal, Portugal(招待講演)
  • Year and Date: 2011-05-09
• [Presentation] Polysaccharide Nanogel DDS for Cancer Immunotherapy (2011)
  • Author(s): K.Akiyoshi
  • Organizer: 1st International Symposium on Carcinogenic Spiral, 9th International Conference on Protein Phosphatase
  • Place of Presentation: Tokyo, Japan(招待講演)
  • Year and Date: 2011-02-02
• [Presentation] ナノゲル工学とドラッグデリバリーシステム (2010)
  • Author(s): 秋吉一成
  • Organizer: 有機化学研究会(白鷺セミナー)第60回講演会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-12-07
• [Presentation] Nanogel Engineering for Protein Drug Delivery System (2010)
  • Author(s): K.Akiyoshi
  • Organizer: 6th Sweden-Japan Workshop on BioNano Technology
  • Place of Presentation: Mishima, Japan(招待講演)
  • Year and Date: 2010-05-13
• [Presentation] ナノゲル基盤マテリアルによる新規タンパク質DDSの開発
  • Author(s): 秋吉一成
  • Organizer: APSTJ2025シンポジウム「バイオとナノが拓く医療イノベーション」
  • Place of Presentation: UDX Gallery NEXT（東京）
  • Invited
• [Presentation] ナノゲルテクトニクスによる新規ソフトマテリアル創製とバイオ応用.
  • Author(s): 秋吉一成
  • Organizer: 第81回高分子若手研究会[関西] 主題 高分子材料が拓くソフトマテリアル化学
  • Place of Presentation: 大坂工業大学（大阪）
  • Invited
• [Presentation] 新規バイオナノトランスポーターの開発とDDS、再生医療応用.
  • Author(s): 秋吉一成
  • Organizer: 第34回日本炎症・再生医学会
  • Place of Presentation: 国立京都国際会館（京都）
  • Invited
• [Book] 遺伝子医学MOOK別冊 ここまで広がるドラッグ徐放技術の最前線 ―古くて新しいドラッグデリバリーシステム(DDS)― (2013)
  • Author(s): 田原義朗，秋吉一成
  • Publisher: メディカルドゥ
• [Book] 先端バイオマテリアルハンドブック (2012)
  • Author(s): 秋吉一成、石原一彦、山岡哲二
  • Total Pages: 580
  • Publisher: NTS 出版
• [Book] 医薬品:薬を運ぶナノキャリアの設計,現代表面科学シリーズ5ひとの暮らしと表面科学 (2011)
  • Author(s): 秋吉一成
  • Publisher: 共立出版
• [Book] ナノゲルエ学によるDDSキャリアの開発と応用,食品・化粧品・医療分野へのゲルの利用 (2010)
  • Author(s): 戸井田さやか, 秋吉一成
  • Publisher: シーエムシー出版
• [Book] ワクチン抗原デリバリーシステム,がん免疫療法-実用化へのチャレンジ- (2010)
  • Author(s): 安岡潤一, 秋吉一成
  • Publisher: シーエムシー出版