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Development of shell molecule for facilitated celluar internalization of the nanoparticle for tumor cells

Research Project

Project/Area Number 15K16331
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionTokyo Institute of Technology

Principal Investigator

Takemoto Hiroyasu  東京工業大学, 科学技術創成研究院, 助教 (10709249)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords生体高分子 / バイオマテリアル / 核酸医薬 / 高分子化学 / ドラッグデリバリーシステム / 高分子科学 / 生体医工学 / 生体材料学
Outline of Final Research Achievements

The chemical structure of the shell molecule in core-shell type nanoparticle is important for regulating biodistribution of the nanoparticle. In this regard, the functionality of the conventional shell molecule is often restricted to stealth ability. Thus, in this study, a new type of shell molecule that facilitates cellular uptake of the nanoparticle in tumorous acidic condition was developed. Consequently, the nanoparticle loading siRNA as an anticancer reagent achieved enhanced cellular uptake efficacy in response to tumorous acidic condition, followed by the potent medicinal effect.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] 天津理工大学(中国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Utility of the 2-nitrobenzenesulfonamide group as a chemical linker for enhanced extracellular stability and cytosolic cleavage in siRNA-conjugated polymer systems2017

    • Author(s)
      C. H. Huang, H. Takemoto, T. Nomoto, K. Tomoda, M. Matsui, N. Nishiyama
    • Journal Title

      ChemMedChem

      Volume: 12 Issue: 1 Pages: 19-22

    • DOI

      10.1002/cmdc.201600488

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] siRNA-loaded polyion complex micelle decorated with charge-conversional polymer tuned to undergo stepwise response to intra-tumoral and intra-endosomal pHs for exerting enhanced RNAi efficacy.2016

    • Author(s)
      M. Tangsangasaksri, H. Takemoto, M. Naito, Y. Maeda, D. Sueyoshi, H. -J. Kim, Y. Miura, J. -Y. Ahn, R. Azuma, N. Nishiyama, K. Miyata, K. Kataoka
    • Journal Title

      Biomacromolecules

      Volume: 17 Issue: 1 Pages: 246-255

    • DOI

      10.1021/acs.biomac.5b01334

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Artificial Control of Gene Silencing Activity Based on siRNA Conjugation with Polymeric Molecule Having Coil Globule Transition Behavior2016

    • Author(s)
      Noor Faizah Che Harun, Hiroyasu Takemoto, Takahiro Nomoto, Keishiro Tomoda, Makoto Matsui, and Nobuhiro Nishiyama
    • Journal Title

      Bioconjugate Chemistry

      Volume: 27 Issue: 9 Pages: 1961-1964

    • DOI

      10.1021/acs.bioconjchem.6b00322

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Influence of RNA strand rigidity on polyion complex formation with block catiomers.2016

    • Author(s)
      K. Hayashi, H. Chaya, S. Fukushima, S. Watanabe, H. Takemoto, K. Osada, N. Nishiyama, K. Miyata, K. Kataoka
    • Journal Title

      Macromol. Rapid Commun.

      Volume: 37 Issue: 6 Pages: 486-493

    • DOI

      10.1002/marc.201500661

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulated protonation of polyaspartamide derivatives bearing repeated aminoethylene side chains for efficient intracellular siRNA delivery with minimal cytotoxicity2015

    • Author(s)
      H. Gao, H. Takemoto, Q. Chen, M. Naito, H. Uchida, X. Liu, K. Miyata, K. Kataoka
    • Journal Title

      Chemical Communications

      Volume: 51 Issue: 15 Pages: 3158-3161

    • DOI

      10.1039/c4cc09859e

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 2-Nitrobenzenesulfonamide group as a chemical linker with highly selective cleavability in response to intracellular redox system for a construction of siRNA-polymer conjugate2017

    • Author(s)
      Hiroyasu Takemoto, Huang Chih-Hao, Takahiro Nomoto, Keishiro Tomoda, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      253rd American Chemical Society National Meeting & Exposition
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2017-04-02
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of stealth shell based on polycarboxybetaine structure tuned to selectively interact with cells in tumor extracellular acidic pH2017

    • Author(s)
      Abdul-Hackam Ranneh, Hiroyasu Takemoto, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Nobohiro Nishiyama
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      宮城県仙台市
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 2-nitrobenzensulfonamide groups as a chemical linker with enhanced extracellular stability and redox-sensitive cleavability for siRNA-conjugated polymer system2016

    • Author(s)
      Patrick Huang, Hiroyasu Takemoto, Takahiro Nomoto, Nobuhiro Nishiyama
    • Organizer
      The 11th SPSJ International Polymer Conference (IPC2016)
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2016-12-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Artificial control of siRNA bioactivity based on the phase transition behavior of the conjugated polymeric molecule2016

    • Author(s)
      Noor Faizah Binti Che Harun, Hiroyasu Takemoto, Takahiro Nomoto, Nobuhiro Nishiyama
    • Organizer
      The 11th SPSJ International Polymer Conference (IPC2016)
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2016-12-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of siRNA-conjugated polymer with coil-globule transition behavior for an artificially controlled gene silencing activity2016

    • Author(s)
      Noor Faizah Binti Che Harun, Hiroyasu Takemoto, Takahiro Nomoto, Nobuhiro Nishiyama
    • Organizer
      第65回高分子討論会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of thermoresponsive polymer-siRNA conjugates for controlled RNAi activity2016

    • Author(s)
      Noor Faizah Binti Che Harun, Hiroyasu Takemoto, Takahiro Nomoto, Nobuhiro Nishiyama
    • Organizer
      第65回高分子学会年次大会
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Accelerated Polymer-siRNA Conjugation Based On Freezing-Thawing Treatment2015

    • Author(s)
      Hiroyasu Takemoto, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka
    • Organizer
      The 11th International Conference on Advanced Polymers via Macromolecular Engineering (APME 2015)
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2015-10-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] PIC型siRNAデリバリーに向けたポリカチオン側鎖構造の改変と細胞内動態制御への展開2015

    • Author(s)
      武元 宏泰、Gao Hui、宮田 完二郎、西山 伸宏、片岡 一則
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      東京都新宿区
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 酸性pH応答性高分子を表層に搭載した高分子ミセルの構築とsiRNAデリバリーへの応用2015

    • Author(s)
      武元 宏泰、宮田 完二郎、タンサガサクスリ モンティラ、内藤 瑞、前田 芳周、キム ヒュンジン、西山 伸宏、片岡 一則
    • Organizer
      第64回高分子学会年次大会
    • Place of Presentation
      北海道札幌市
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] pH応答性ポリマー及び薬物送達システム2016

    • Inventor(s)
      武元宏泰 他5名
    • Industrial Property Rights Holder
      武元宏泰 他5名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-12-15
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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