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Synthesis and evaluation of peptide-mimetic anti-cancer nanoparticles

Research Project

Project/Area Number 18K18380
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionHiroshima University

Principal Investigator

Takahashi Haruko  広島大学, 統合生命科学研究科(理), 助教 (70775767)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords抗がん性ポリマー / ドーマント / がん微小環境 / バイオミメティクス / がん微小環境モデル / 合成高分子 / 抗がん剤 / ナノ粒子 / 抗がん性 / 固形がん
Outline of Final Research Achievements

The discovery of anti-cancer agents effective against non-proliferative dormant cancer cells is a significant challenge in cancer biology and drug development fields because currently used drugs target only actively proliferating cancer cells. We have developed new anti-cancer polymers that mimic the mode of action of host-defense peptides (HDPs) with anticancer activity. These polymers are synthetic methacrylate polymers with cationic and amphiphilic properties to recapitulate the biophysical traits of the HDPs. We designed the polymer compositions and structures to target highly expressed anionic lipids exposed on the cancer cells and act by disrupting the integrity of cancer cell membranes, causing cell death. Because this mechanism is not dependent on cell proliferation, our polymers have shown potent activity against dormant cancer cells and in vitro 3D tumor models. Our new polymer design approach has paved the way for discovery of novel anti-cancer therapeutics.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、生体のペプチドを模倣することより、「固形がんの深部まで到達可能」で、固形がん内の「休眠状態(ドーマント)のがんにも有効」な新しい抗がん性ポリマーの設計指針を確立した。この抗がん性ポリマーは、従来の抗がん薬とは異なり、がん細胞膜にアタックする機構を利用した、ポリマーならではの機能を利用した次世代の抗がん性マテリアルとして高いポテンシャルが期待できる。これにより、これまで治療の難しかった固形がん中のドーマントながん細胞に対する、新しいアプローチ法を提案することができた。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2019 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Int'l Joint Research] ミシガン大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Anticancer polymers designed for killing dormant prostate cancer cells.2019

    • Author(s)
      Takahashi, T., Yumoto, K., Yasuhara, K., Enrico T. Nadres, T.E., Kikuchi, Y., Taichman, R.S., and Kuroda, K.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1096-1096

    • DOI

      10.1038/s41598-018-36608-5

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular engineering of antimicrobial polymers to target biofilms2019

    • Author(s)
      Haruko Takahashi
    • Organizer
      ACS 257th National Meeting & Exposition
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト細胞の3次元培養によるがん微小環境の構築と解析2019

    • Author(s)
      高橋治子
    • Organizer
      第71回 日本生物工学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 3次元in vitro培養系によるがん微小環境理解のための組織構成的アプローチ2019

    • Author(s)
      高橋治子, 菊池裕
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2021-02-19  

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