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pH応答性炭酸アパタイトナノ粒子を用いたES細胞の分化制御

Research Project

Project/Area Number 11F01350
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field Biomedical engineering/Biological material science
Research InstitutionTokyo Institute of Technology

Principal Investigator

赤池 敏宏  東京工業大学, 大学院生命理工学研究科, 特任教授

Co-Investigator(Kenkyū-buntansha) HOSSAIN Md. Shariff  東京工業大学, 大学院生命理工学研究科, 外国人特別研究員
HOSSAIN M.S.  東京工業大学, 大学院・生命理工学研究科, 外国人特別研究員
HOSSAIN Md.Sharif  東京工業大学, フロンティア研究機構, 外国人特別研究員
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2013: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2012: ¥800,000 (Direct Cost: ¥800,000)
Keywords炭酸アパタイトナノ粒子 / pH応答性ナノ粒子 / 制癌剤のドラッグデリバリー / ドキソルビシン / E-カドヘリン-Fcキメラタンパク / ソノーティング効果 / iPS細胞の非ウィルス的作製法 / Si-RNAデリバリー / 炭酸アパタイト / ES/iPS細胞 / si-RNAデリバリー / E-カドヘリンFcキメラタンパク質 / 細胞用まな板 / Cell-Cooking Plate / 細胞認識性マトリックス / ES細胞 / siRNA / ドキソルビシン-炭酸アパタイトナノ粒子複合体 / E-カドヘリン・Fcキメラタンパク質
Research Abstract

大阪大学医学部一消化器外科グループとの共同研究で炭酸アパタイト微粒子を200~300nmサイズ以下にまで微細化させることに成功し、これらのナノ粒子の調整時に加えられたドキソルビシン(Dox)や各種DNA、siRNAが定量的に担持されること、さらにそれらのナノ粒子が既に報告済みのpH応答的崩壊と包摂分子の細胞(リボソーム)内放出を示すことを定量的に確認した。これらの①取り込み②細胞内挙動③生理活性発現メカニズム④放出カルシウムの細胞外排出等のプロセスの解析も行った。消化器がん治療等の臨床において使用されるドキソルビシン(DOX)包摂の炭酸アパタイトはin vitro細胞内での取り込みと迅速なpH応答性、分解・放出を経てフリーなDOXの投与の場合より圧倒的に効率的に腫瘍を縮小させ延命効果を発揮させた。(Nature Co㎜unication再審査中)また当研究室(S. Hossainグループ)のもう一つの独創的技術であるカドヘリンキメラタンパク、各種合成糖質高分子等々の新規の細胞接着用マトリックス設計論(マトリックス工学)を応用し、ips細胞作製に通常用いられるマウス胎児繊維芽細胞に対して炭酸アパタイトナノ粒子による遺伝子導入を試みた。細胞マトリックスの一種であるフィブロネクチンをコートした炭酸アパタイトナノ粒子を用いると、遺伝子導入の従来のいかなる方法よりも効率的にips細胞を作成することが出来た。次に当研究室で設計・開発されたE-カドヘリン―Fcキメラタンパク質をコートしたディッシュに前述の成功裏に出現したips細胞コロニーを移し替え、E-カドヘリン―Fcマトリックスのソーティング効果を検討した。E-カドヘリンを発現するiPS細胞のみが接着および増殖した。これはiPS細胞にマトリックス工学を応用した細胞ソーティングの最初の成功例となった。

Strategy for Future Research Activity

(抄録なし)

Report

(3 results)
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (13 results)

All 2013 2012 2011

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (6 results) Book (2 results)

  • [Journal Article] PKC activation promotes internalization of DNA-immobilized inorganic nano-crystals by clathrin-dependent endocytosis for efficient transgene exnression in human lymphocytes2013

    • Author(s)
      Nag K^*, Hossain S^* (^*equal first author), Naznin S, Chowdhury EH
    • Journal Title

      J. of Nanomed. and Nanotech.

      Volume: (In Press) Issue: 04

    • DOI

      10.4172/2157-7439.1000174

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bile Acids Increase Levels of microRNAs 221 and 222, Leading to Degradation of CDX2 During Esophageal Carcinogenesis2013

    • Author(s)
      J. Matsuzaki, H. Suzuki, H. Tsugawa, M. Watanabe, S. Hossain, T. Akaike, T. Hibi, et. al.
    • Journal Title

      Gastroenterology

      Volume: (In Press) Issue: 6 Pages: 1300-1311

    • DOI

      10.1053/j.gastro.2013.08.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication and intracellular delivery of Doxorubicin/Carbonate Apatite Nanocomposites : Effiect on growth retardation of established Colon Tumor.2013

    • Author(s)
      Hossain S, Yamamoto H, Chowdhury EH, Wu x, Akaike T, et.al
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e60428-e60428

    • DOI

      10.1371/journal.pone.0060428

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel,2012

    • Author(s)
      Stanislaus A, Bakhtiar A, Salleh D, Hossain S, Akaike T, Chowdhury EH, et.al
    • Journal Title

      Cancer Cell Int.

      Volume: 12 Issue: 1 Pages: 30-30

    • DOI

      10.1186/1475-2867-12-30

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nanoparticles and toxicity in therapeutic delivery : the ongoing debate2011

    • Author(s)
      Hossain S, Chowdhury EH, Akaike T
    • Journal Title

      Therapeutic Deliv.

      Volume: 2(2) Pages: 125-132

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] pH-sensitive Nano-crystals of Carbonate Apatite for Smart and Efficent Drug/transgene Delivery2013

    • Author(s)
      Sharif Hossain, T. Akaike
    • Organizer
      40th Annual Meeting & Exposition of the Controlled Release Society (CRS)
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2013-07-22
    • Related Report
      2013 Annual Research Report
  • [Presentation] Establishment of 3D culture system for primary hepatocytes, 'Regulation of cell membrane polarity for tissue engineering'2012

    • Author(s)
      K. Arai, T. Adachi, S. Hossain, T. Akaike, M. Nakamura,
    • Organizer
      3rd TERMIS World Congress 2012
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Intracellular Regulation of ES/iPS Cells on E-Cad-Fc Engineered Matrix facilitated by Bio-functionalized Nanoparticles of Carbonate Apatite2012

    • Author(s)
      S. Hossain and T. Akaike,
    • Organizer
      3rd TERMIS World Congress 2012
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2012-09-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] Bio-functionalized pH-sensitive Carbonate Apatite Nanoparticles Facilitated Intracellular Regulation of ES/iPS Cells on E-Cad-Fc Engineered Matrix,2012

    • Author(s)
      Sharif Hossain and Toshihiro Akaike
    • Organizer
      39th Annual Meeting & Exposition of the Controlled Release Society (CRS),
    • Place of Presentation
      Quebec City, Canada.
    • Year and Date
      2012-06-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] Novel pH-sensitive Carbonate Apatite Nanoparticles as Intracellular Gene/Drug Transporter,2012

    • Author(s)
      Sharif Hossain and Toshihiro Akaike
    • Organizer
      39th Annual Meeting & Exposition of the Controlled Release Society (CRS),
    • Place of Presentation
      Quebec City, Canada.
    • Year and Date
      2012-06-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] Design of Super Effective pH-sensitive Carbonate Apatite Nanoparticles as Intracellular Gene/Drug Transporter2011

    • Author(s)
      Hossain S, Akaike T
    • Organizer
      The 3rd Asian Biomaterials Congress
    • Place of Presentation
      Busan, South Korea
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Book] Bioengineered Nanomaterials2013

    • Author(s)
      Sharif Hossain, Ezharul Hoque Chowdhury, Toshihiro Akaike
    • Publisher
      Inorganic Nanomaterials of Carbonate apatite as intracellular nucleic acid/drug transporters
    • Related Report
      2013 Annual Research Report
  • [Book] Bioengineered Nanomaterials, Chapter Title : Inorganic Nanomaterials of Carbonate apatite as intracellular nucleic acid/drug transporters,2013

    • Author(s)
      Sharif Hossain, Ezharul Hoque Chowdhury and Toshihiro Akaike
    • Publisher
      Taylor & Francis Publisher,(In Press)
    • Related Report
      2012 Annual Research Report

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Published: 2013-04-25   Modified: 2024-03-26  

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