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Nanoparticle-induced local membrane potential enhancement to form nanoscale pore in cell membrane

Research Project

Project/Area Number 19K22976
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionOsaka Prefecture University

Principal Investigator

Nakamura Hideya  大阪府立大学, 工学(系)研究科(研究院), 准教授 (00584426)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Keywords細胞膜透過 / 細胞内導入 / ナノ粒子 / 細胞膜 / ナノバイオ界面
Outline of Research at the Start

細胞にダメージを与えずに、細胞の中に化合物を効率よく送達できれば、究極の細胞内送達手法となる。本研究では、申請者が最近見出した「ナノ粒子が誘起する局所膜電位増強によって細胞膜にナノ細孔があく」新奇な現象を利用して、細胞にとって無痛針のような究極の低侵襲送達手法の萌芽に挑戦する。検討では、平面脂質膜法と顕微鏡観察を組み合わせた実験系を独自に構築して実験を行う。同時に、分子動力学計算でナノ粒子と細胞膜の界面電気現象を解析する。本研究は、この前人未踏のナノスケール細胞膜穿孔を、ナノ粒子が誘起する局所膜電位増強で実現する、これまでになかった独自の戦略・考え方に基づいた挑戦的研究である。

Outline of Final Research Achievements

We have found that even by a weak electric field, charged nanoparticles (NPs) can translocate across the cell membrane via non-disruptive pathway due to local enhancement of the membrane potential by adhesion of charged NPs. In this study, we hypothesized that this local enhancement of the membrane potential can facilitate the translocation of an extracellular substance across a cell membrane. We investigated our hypothesis by experiments using an artificial cell membrane system. A phospholipid bilayer, which is a main component of biological cell membrane, was prepared by a droplet contact method. As a result, translocation of model delivery substance (dextran) was confirmed by using a weak external electric field, which was lower than the membrane breakdown potential, with charged nanoparticles. Consequently, it was suggested that by combining the weak external electric field with charged nanoparticles the cell membrane permeability can be enhanced.

Academic Significance and Societal Importance of the Research Achievements

細胞の外から中に化合物を送達する技術は、再生医療用細胞やバイオ医薬品製造など多くの医工学分野において重要な技術である。この際、細胞にダメージを与えずに、送達化合物が細胞膜を透過し、細胞内に送達されることが理想である。本研究は、微弱な電位とナノ粒子の電荷を重ね合わせることで引き起こされる局所膜電位増強を利用して、ナノスケールの細孔を開け、低侵襲での細胞外物質送達を検討した。その結果、ナノ粒子存在下で微弱な電場を印加することで膜の透過性が向上することを観測した。また、物質透過前後で膜の質が同等であることから低侵襲な物質の膜透過が示唆された。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Int'l Joint Research] Cleveland Clinic(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Direct translocation of a negatively charged nanoparticle across a negatively charged model cell membrane2021

    • Author(s)
      Y. Ikeda, H. Nakamura, S. Ohsaki, S. Watano
    • Journal Title

      Physical Chemistry Chemical Physics

      Volume: in press Issue: 17 Pages: 1-8

    • DOI

      10.1039/d0cp06278b

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Translocation of Nanoparticle across Cell Membrane under Weak External Electric Field2020

    • Author(s)
      仲村英也
    • Journal Title

      Journal of the Society of Powder Technology, Japan

      Volume: 57 Issue: 1 Pages: 25-30

    • DOI

      10.4164/sptj.57.25

    • NAID

      130007801262

    • ISSN
      0386-6157, 1883-7239
    • Year and Date
      2020-01-10
    • Related Report
      2019 Research-status Report
  • [Journal Article] Direct translocation of nanoparticles across a model cell membrane by nanoparticle-induced local enhancement of membrane potential2019

    • Author(s)
      Hideya Nakamura, Kyohei Sezawa, Masataka Hata, Shuji Ohsaki and Satoru Watano
    • Journal Title

      Physical Chemistry Chemical Physics

      Volume: 21 Issue: 35 Pages: 18830-18838

    • DOI

      10.1039/c9cp02935d

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] アルカンチオール修飾金ナノ粒子の粒子設計と細胞膜透過との関係2021

    • Author(s)
      溝奥 朱音,仲村 英也,大崎 修司,綿野 哲
    • Organizer
      化学工学会第86年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ナノ粒子と微弱な電場印加を利用した細胞膜透過性の向上2020

    • Author(s)
      岡村 拓海, 仲村 英也, 大崎 修司, 綿野 哲
    • Organizer
      化学工学会第51回秋季大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ナノ粒子と微弱な電場印加を利用した細胞膜透過性の向上2020

    • Author(s)
      岡村拓海,仲村英也,大崎修司,綿野哲
    • Organizer
      化学工学会第85年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ナノ粒子の細胞膜直接透過現象の解析と制御2019

    • Author(s)
      仲村英也
    • Organizer
      材料化学システム工学討論会2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ナノ粒子の細胞膜透過性を評価します2019

    • Author(s)
      仲村英也
    • Organizer
      APPIE産学連携フェア2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Direct translocation of nanoparticle across model cell membrane by nanoparticle-induced local enhancement of membrane potential2019

    • Author(s)
      Hideya Nakamura, Kyohei Sezawa, Masataka Hata, Shuji Ohsaki, Satoru Watano
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Experimental investigation of nanoparticle translocation across cell membrane under weak electric potential2019

    • Author(s)
      Masataka Hata, Hideya Nakamura, Shyuji Ohsaki, Satoru Watano
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Direct translocation of negatively charged nanoparticle across negatively charged cell membrane2019

    • Author(s)
      Yoko Ikeda, Hideya Nakamura, Shuji Ohsaki, Satoru Watano
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-07-04   Modified: 2022-01-27  

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