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Functional polymer that recognizes tumorous pH for effective delivery of the coated nanoparticles to tumor tissues

Research Project

Project/Area Number 17H04743
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
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) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2019: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2018: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords生体高分子 / バイオマテリアル / 薬物送達システム / 高分子 / 刺激応答材料 / 生体材料 / 高分子構造・物性
Outline of Final Research Achievements

Nanoparticles have been employed as a delivery vehicle to tumor tissues. In this regard, I developed a new design of coating polymers for regulating the biodistribution of the nanoparticles. In general, coating polymers suppress accumulation of the nanoparticles in normal tissues, and avoid immune responses for blood retention of the nanoparticles. However, the stealth property of the coating polymers often decrease the interaction with tumor tissues and decelerate internalization by cancer cells. Thus, in the present study, a functional polymer that switches its property to be tissue-interactive in response to tumorous pH was developed. The developed polymer realized similar biodistribution of the coated nanoparticle for normal tissues, while the the tumor accumulation level was three times higher, relative to PEG system.

Academic Significance and Societal Importance of the Research Achievements

がんの化学療法において、制がん剤の体内動態制御は低い副作用と高い治療効果の双方の観点から重要である。既存のシェル分子による体内動態制御は血液成分及び正常組織との相互作用の抑制に限定されており、腫瘍組織での制がん剤の細胞取り込みを促進する機能は兼備されていない。本研究はこういった現状を打破することに成功し、その両立に成功した。さらに本研究は、新規シェル分子の開発を通して、制がん剤の腫瘍組織への送達に関する新たな方針を提案するものであるため、今後の薬物創製に対して多大なる影響を与えることが必至であり、その分野の飛躍的な発展へと大いに寄与するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (18 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] Sohag University(Egypt)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Polymeric modification of gemcitabine via cyclic acetal linkage for enhanced anticancer potency with negligible side effects2020

    • Author(s)
      Takemoto Hiroyasu、Inaba Takanori、Nomoto Takahiro、Matsui Makoto、Liu Xiaomeng、Toyoda Masahiro、Honda Yuto、Taniwaki Kaori、Yamada Naoki、Kim Junhyun、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomaterials

      Volume: 235 Pages: 119804-119804

    • DOI

      10.1016/j.biomaterials.2020.119804

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly(vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism2020

    • Author(s)
      Nomoto Takahiro、Inoue Yukiya、Yao Ying、Suzuki Minoru、Kanamori Kaito、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Science Advances

      Volume: 6 Issue: 4

    • DOI

      10.1126/sciadv.aaz1722

    • NAID

      120006779811

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pyruvate Responsiveness Based on α-Oxohydrazone Formation for Intracellular siRNA Release from Polyion Complex-Based Carriers2019

    • Author(s)
      Takemoto Hiroyasu、Wang Chih-Ling、Nomoto Takahiro、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 6 Pages: 2305-2314

    • DOI

      10.1021/acs.biomac.9b00261

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers2019

    • Author(s)
      Watanabe Sumiyo、Hayashi Kotaro、Toh Kazuko、Kim Hyun Jin、Liu Xueying、Chaya Hiroyuki、Fukushima Shigeto、Katsushima Keisuke、Kondo Yutaka、Uchida Satoshi、Ogura Satomi、Nomoto Takahiro、et al.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1894-1894

    • DOI

      10.1038/s41467-019-09856-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Poly(N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety2018

    • Author(s)
      Muttaqien Sjaikhurrizal El、Nomoto Takahiro、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Biomacromolecules

      Volume: 20 Issue: 4 Pages: 1493-1504

    • DOI

      10.1021/acs.biomac.8b01465

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of multiple cyclic RGD peptides on tumor accumulation and intratumoral distribution of IRDye 700DX-conjugated polymers2018

    • Author(s)
      Dou Xuebo、Nomoto Takahiro、Takemoto Hiroyasu、Matsui Makoto、Tomoda Keishiro、Nishiyama Nobuhiro
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 8126-8126

    • DOI

      10.1038/s41598-018-26593-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Ethylenediamine‐based Switch to Render the Polyzwitterion Cationic at Tumorous pH for Effective Tumor Accumulation of Coated Nanomaterials2018

    • Author(s)
      Abdul-Hackam Ranneh, Hiroyasu Takemoto, Shunya Sakuma, Aziz Awaad, Takahiro Nomoto, Yuki Mochida, Makoto Matsui, Keishiro Tomoda, Mitsuru Naito, Nobuhiro Nishiyama
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 57 Issue: 18 Pages: 5057-5061

    • DOI

      10.1002/anie.201801641

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional polymer-based siRNA delivery carrier that recognizes site-specific biosignals2017

    • Author(s)
      Hiroyasu Takemoto, Nobuhiro Nishiyama
    • Journal Title

      Journal of Controlled Release

      Volume: 267 Pages: 90-99

    • DOI

      10.1016/j.jconrel.2017.09.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] The development of polyzwitterion that responds to tumorous pH for effective delivery of nanomaterials to the deeper site in the tumor tissue2020

    • Author(s)
      Hiroyasu Takemoto, Aziz Awaad, Takahiro Nomoto, Makoto Matsui, Yutaka Miura, Nobuhiro Nishiyama
    • Organizer
      ACS Spring 2020 National Meeting & Expo
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Polyzwitterion comprising 1,2-diaminoethane that recognizes tumorous pH for effective delivery of the coated nanoparticles2019

    • Author(s)
      Hiroyasu Takemoto, Nobuhiro Nishiyama
    • Organizer
      ICBZM2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍pH応答性高分子べタインの開発と ナノ粒子のがん送達への展開2019

    • Author(s)
      武元宏泰,Awaad Aziz,Ranneh Abdul-Hackam,野本貴大,松井誠,三浦裕,西山伸宏
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍内pH応答性高分子ベタインの設計と 被覆ナノ粒子への展開2019

    • Author(s)
      武元宏泰,Awaad Aziz,Ranneh Abdul-Hackam,野本貴大,松井誠,三浦裕,西山伸宏
    • Organizer
      第68回高分子学会討論会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Ethylenediamine-based betaine structure switches the neutral net charge of polyzwitterion into cationic at tumorous pH toward effective tumor accumulation of the coated nanomaterials2018

    • Author(s)
      Hiroyasu Takemoto, Abduhl Hackam Ranneh, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Nobuhiro Nishiyama
    • Organizer
      256th ACS National Meeting & Exposition
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ethylenediamine-based polyzwitterion that becomes cationic at tumorous pH for effective tumor accumulation of the coated nanomaterials2018

    • Author(s)
      Hiroyasu Takemoto, Abdul-Hackam Ranneh, Takahiro Nomoto, Makoto Matsui, Nobuhiro Nishiyama
    • Organizer
      The 12th SPSJ International Polymer Conference (IPC2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bioresponsive Polyzwitterion that Recognizes Tumorous pH for a Construction of Tumor-Targeted Carriers2018

    • Author(s)
      Hiroyasu Takemoto
    • Organizer
      The 35th International Conference of Photopolymer Science and Technology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] エチレンジアミン構造に基づく高分子ベタインの電荷制御とナノ粒子の腫瘍送達への展開

    • URL

      http://www.res.titech.ac.jp/news/reserch/201806nt.html

    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] pH応答性ポリマー及び薬物送達システム2017

    • 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
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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