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Development of enzyme-loaded PIC-nanoreactor working under the blood circulation

Research Project

Project/Area Number 15K12536
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionThe University of Tokyo

Principal Investigator

Anraku Yasutaka  東京大学, 大学院工学系研究科(工学部), 助教 (60581585)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords酵素 / 酵素補充療法 / 薬剤送達システム / 高分子ベシクル / 急性リンパ性白血病 / 高分子化学 / ナノリアクタ / 急性骨髄性白血病 / 急性白血病 / ドラッグデリバリーシステム / PICsome
Outline of Final Research Achievements

Enzyme-loaded synthetic vesicles have attracted great attention for their feasibility to exert the efficient and prolonged functionality of loaded enzymes in harsh environments. However, several issues remain regarding the optimization of their structures toward practical application. Herein, we fabricated polyion complex vesicles loaded with L-asparaginase (ASNase@PICsomes) and conducted a detailed characterization to ensure their utility as nanoreactors functioning under the harsh in vivo environment (bloodstream). ASNase@PICsomes showed 100 nm-sized monodispersed vesicular structures. Fluorescence cross-correlation spectroscopy revealed essentially no empty PICsome fraction in the product, indicating the quantitative formation of ASNase@PICsomes. Furthermore, ASNase@PICsomes exhibited significantly prolonged enzymatic reaction compared with free ASNase after systemic injection into mice, corroborating their functionality as in vivo nanoreactors working under the blood circulation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (38 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 14 results,  Invited: 2 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Therapeutic Vesicular Nanoreactors with Tumor-Specific Activation and Self-Destruction for Synergistic Tumor Ablation2017

    • Author(s)
      Li Junjie、Dirisala Anjaneyulu、Ge Zhishen、Wang Yuheng、Yin Wei、Ke Wendong、Toh Kazuko、Xie Jinbing、Matsumoto Yu、Anraku Yasutaka、Osada Kensuke、Kataoka Kazunori
    • Journal Title

      Angew Chem Int Ed Engl

      Volume: 56 Issue: 45 Pages: 14025-14030

    • DOI

      10.1002/anie.201706964

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Facile Preparation of Delivery Platform of Water-Soluble Low-Molecular-Weight Drugs Based on Polyion Complex Vesicle (PICsome) Encapsulating Mesoporous Silica Nanoparticle2017

    • Author(s)
      2.Akinori Goto, Hung-Chi Yen, Yasutaka Anraku, Shigeto Fukushima, Ping-Shan Lai, Masaru Kato, Akihiro Kishimura, and Kazunori Kataoka
    • Journal Title

      ACS Biomater. Sci. Eng.

      Volume: 印刷中 Issue: 5 Pages: 807-815

    • DOI

      10.1021/acsbiomaterials.6b00562

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Enzyme-Loaded Polyion Complex Vesicles as in Vivo Nanoreactors Working Sustainably under the Blood Circulation: Characterization and Functional Evaluation2017

    • Author(s)
      Daiki Sueyoshi, Yasutaka Anraku, Toru Komatsu, Yasuteru Urano and Kazunori Kataoka
    • Journal Title

      Biomacromolecules

      Volume: 18 Issue: 4 Pages: 1189-1196

    • DOI

      10.1021/acs.biomac.6b01870

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systemically injectable enzyme-loaded polyion complex vesicles as in vivo nanoreactors functioning in tumors2016

    • Author(s)
      Y. Anraku, A. Kishimura, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, S. Fukushima, D. Sueyoshi, M. R. Kano, Y. Urano, N. Nishiyama, K. Kataoka
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 128 Issue: 2 Pages: 570-575

    • DOI

      10.1002/ange.201508339

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enhanced target recognition of nanoparticles by cocktail PEGylation with chains of varying lengths2016

    • Author(s)
      T. Ishii, K. Miyata, Y. Anraku, M. Naito, Y. Yi, T. Jinbo, S. Takae, Y. Fukusato, M. Hori, K. Osada, K. Kataoka
    • Journal Title

      Chem. Commun.

      Volume: 52 Issue: 7 Pages: 1517-1519

    • DOI

      10.1039/c5cc06661a

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Enzyme-loaded polyion complex vesicles as in vivo nanoreactors2017

    • Author(s)
      Y. Anraku
    • Organizer
      11th Annual Symposium on Nanobiotechnology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PIC vesicle-based enzymatic nanoreactors functioning in vivo under the blood circulation2017

    • Author(s)
      D. Sueyoshi, Y. Anraku, T. Komatsu, Y. Urano, K. Kataoka
    • Organizer
      11th Annual Symposium on Nanobiotechnology 2017
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stabilization and application of polyion complex vesicles (PICsomes) with chemical modifications of polymer side-chain2017

    • Author(s)
      M. Hori, Y. Anraku, C. Horacio, A. Kishimura, K. Kataoka
    • Organizer
      The 14th US-Japan Symposium on Drug Delivery Systems Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多点ではたらくイオン間相互作用と水素結合を利用した自己組織化によるポリマーソームの構築とその特性解析2017

    • Author(s)
      堀真緒、安楽泰孝、岸村顕広、片岡一則
    • Organizer
      第66回高分子討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血流中で機能するナノリアクターを指向した酵素封入ポリイオンコンプレックス型ベシクルの構築および機能評価2016

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第25回インテリジェント材料・システムシンポジウム
    • Place of Presentation
      東京女子医科大学、新宿区、東京都
    • Year and Date
      2016-01-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 生体内環境での安定性向上を目指したポリイオンコンプレックス型ベシクル(PICsome)の開発2016

    • Author(s)
      堀真緒、安楽泰孝、岸村顕広、片岡一則
    • Organizer
      遺伝子・デリバリー研究会第16回シンポジウム
    • Place of Presentation
      川崎生命科学・環境研究センター、川崎市、神奈川県
    • Related Report
      2016 Research-status Report
  • [Presentation] 血中循環型ナノリアクターを指向した酵素封入PICsomeの開発2016

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      遺伝子・デリバリー研究会第16回シンポジウム
    • Place of Presentation
      川崎生命科学・環境研究センター、川崎市、神奈川県
    • Related Report
      2016 Research-status Report
  • [Presentation] 血流中に持続的なナノ反応場を提供する酵素封入PIC型ベシクルの開発2016

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第65回高分子学会年次大会
    • Place of Presentation
      神戸国際会議場・展示場、神戸市、兵庫県
    • Related Report
      2016 Research-status Report
  • [Presentation] 内水相に酵素を封入したPIC型ベシクルの血中循環型ナノリアクターとしての機能展開2016

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第32回DDS学会学術大会
    • Place of Presentation
      グランシップ(静岡県コンベンションアーツセンター)、静岡市、静岡県
    • Related Report
      2016 Research-status Report
  • [Presentation] ポリイオンコンプレックス型ベシクル(PICsome)の開発とその物性評価2016

    • Author(s)
      堀真緒、安楽泰孝、岸村顕広、片岡一則
    • Organizer
      西日本ナノシート研究会サマーキャンプ2016
    • Place of Presentation
      シーサイドホテル屋久島、屋久島町、鹿児島県
    • Related Report
      2016 Research-status Report
  • [Presentation] 血中循環型ナノリアクターを指向した酵素封入PIC型ベシクルの物性および機能評価2016

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第65回高分子討論会
    • Place of Presentation
      神奈川大学横浜キャンパス、横浜市、神奈川県
    • Related Report
      2016 Research-status Report
  • [Presentation] Development of polyion complex vesicles (PICsomes) with various side-chain modifications for stability enhancement under the physiological salt condition2016

    • Author(s)
      M. Hori, Y. Anraku, A. Kishimura, K. Kataoka
    • Organizer
      2016 MRS Fall Meeting & Exhibit
    • Place of Presentation
      Boston, Massachussets, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of enzyme-loaded PIC vesicles for enzyme/prodrug therapy2016

    • Author(s)
      Y. Anraku, A. Kishimura, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, M. R. Kano, Y. Urano, N. Nishiyama, K. Kataoka
    • Organizer
      Frontiers2016 Symposium of the EPFL
    • Place of Presentation
      Swiss Federal Institute of Technology(EPFL), Lausanne, Switzerland
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of polyion complex vesicles (PICsomes) with side chain modification as new drug delivery carrier2016

    • Author(s)
      M. Hori, Y. Anraku, S. Chuanoi, A. Kishimura, K. Kataoka
    • Organizer
      Frontiers2016 Symposium of the EPFL
    • Place of Presentation
      Swiss Federal Institute of Technology(EPFL), Lausanne, Switzerland
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enzyme-loaded polyion complex vesicles as nano-reactors functioning in the blood circulation2016

    • Author(s)
      D. Sueyoshi, Y. Anraku, K. Kataoka
    • Organizer
      The 11th SPSJ International Polymer Conference (IPC2016)
    • Place of Presentation
      Fukuoka International Confress Center, Fukuoka
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of polyion complex vesicle (PICsome) decorated with guanidinium groups as a new drug delivery carrier2015

    • Author(s)
      M. Hori, Y. Anraku, S. Chuanoi, A. Kishimura, K. Kataoka
    • Organizer
      The 13th US-Japan Symposium on Drug Delivery Systems Conference
    • Place of Presentation
      The Westin Maui Resort & Spa, Hawaii, USA
    • Year and Date
      2015-12-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of enzyme-loaded polyion complex vesicles for in vivo nanoreactor2015

    • Author(s)
      Y. Anraku, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, S. Fukushima, D. Sueyoshi, A. Kishimura, M. Kano, Y. Urano, N. Nishiyama, K. Kataoka
    • Organizer
      THE INTERNATIONAL CHEMICAL CONGRESS OF PACIFIC BASIN SOCIETIES (PACIFICHEM2015)
    • Place of Presentation
      Hawaii Convention Center, Hawaii, USA
    • Year and Date
      2015-12-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stability enhancement of polyion complex vesicles (PICsomes) by polymer side-chain modification2015

    • Author(s)
      M. Hori, Y. Anraku, S. Chuanoi, A. Kishimura, K. Kataoka
    • Organizer
      PPC-14 14th PACIFIC POLYMER CONFERENCE
    • Place of Presentation
      Kauai, Hawaii, USA
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of enzyme-loaded PIC nanoreactor for enzyme/prodrug therapy2015

    • Author(s)
      Y. Anraku, A. Kishimura, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, S. Fukushima, D. Sueyoshi, M. R. Kano, Y. Urano, N. Nishiyama, K. Kataoka
    • Organizer
      PPC-14 14th PACIFIC POLYMER CONFERENCE
    • Place of Presentation
      Kauai, Hawaii, USA
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of enzyme-loaded polyion complex vesicles as versatile nano-reactors in blood circulation2015

    • Author(s)
      D. Sueyoshi, Y. Anraku, K. Kataoka
    • Organizer
      2015 MRS Fall Meeting & Exhibit
    • Place of Presentation
      Boston, Massachussets, USA
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生体内ナノリアクターとしての酵素封入PIC型ベシクルの構築および血流中における機能評価2015

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第37回日本バイオマテリアル学会大会
    • Place of Presentation
      京都テルサ、京都市、京都府
    • Year and Date
      2015-11-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of polyion complex vesicles (PICsomes) functionalized by guanidinium moieties2015

    • Author(s)
      M. Hori, Y. Anraku, A. Kishimura, K. Kataoka
    • Organizer
      Core2Core LMU-UTokyo Symposium 2015
    • Place of Presentation
      Innovation Center for Biotechnology (IZB), Planegg/Martinsried, Deutschland
    • Year and Date
      2015-10-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血流中で機能するナノリアクターとしての酵素封入PIC型ベシクルの構築および機能評価2015

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第64回高分子討論会
    • Place of Presentation
      東北大学川内キャンパス、仙台市、宮城県
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Self-assembled nanostructures from block copolymers for biomedical application2015

    • Author(s)
      Y. Anraku
    • Organizer
      250th American Chemical Society (ACS) National Meeting & Exposition
    • Place of Presentation
      Boston, Massachusetts, USA
    • Year and Date
      2015-08-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 血流中で機能する酵素封入PIC型ナノリアクターの開発2015

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      京王プラザホテル、新宿区、東京都
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 血流中で機能するナノリアクターを指向した酵素封入PIC型ベシクルの構築2015

    • Author(s)
      末吉大輝、安楽泰孝、片岡一則
    • Organizer
      第64回高分子学会年次大会
    • Place of Presentation
      札幌コンベンションセンター、札幌市、北海道
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
  • [Presentation] PIC型ベシクルの特異な物質透過性に関する機能評価2015

    • Author(s)
      安楽泰孝、O. Mutaf、岸村顕広、片岡一則
    • Organizer
      第64回高分子学会年次大会
    • Place of Presentation
      札幌コンベンションセンター、札幌市、北海道
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
  • [Book] 分子マシンの科学2017

    • Author(s)
      安楽泰孝、片岡一則
    • Total Pages
      200
    • Publisher
      化学同人
    • ISBN
      9784759813869
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学大学院工学系研究科 カブラル研究室

    • URL

      http://www.bmc.t.u-tokyo.ac.jp

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学大学院工学系研究科バイオエンジニアリング専攻カブラル研究室

    • URL

      http://www.bmc.t.u-tokyo.ac.jp

    • Related Report
      2016 Research-status Report
  • [Remarks] 片岡研究室ホームページ

    • URL

      http://www.bmw.t.u-tokyo.ac.jp

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] ポリイオンコンプレックス型ポリマーソームを用いたナノリアクタとその製造方法2016

    • Inventor(s)
      片岡一則、安楽泰孝、末吉大輝
    • Industrial Property Rights Holder
      片岡一則、安楽泰孝、末吉大輝
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-05-06
    • Related Report
      2016 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] ポリイオンコンプレックス型ポリマーソームを用いたナノリアクタとその製造方法2015

    • Inventor(s)
      片岡一則、安楽泰孝、末吉大輝
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-095278
    • Filing Date
      2015-05-07
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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