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Remote Control of Insulin Concentration in blood by Zinc pDNA Quaternary Complexes for New Diabetes Therapy

Research Project

Project/Area Number 16K12899
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionTokyo Metropolitan University

Principal Investigator

Asayama Shoichiro  首都大学東京, 都市環境科学研究科, 准教授 (90315755)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords薬物送達システム / 亜鉛イオン / 核酸 / 糖尿病治療
Outline of Final Research Achievements

From a chemical structure perspective, ethylated PVIm (PVIm-Et) chelated the most Zn2+ ions compared to methylated PVIm (PVIm-Me) and butylated PVIm (PVIm-Bu). The resulting Zn2+-chelated PVIm-Et formed more stable complexes with plasmid DNA (pDNA) complex than non-chelated PVIm-Et. The Zn2+-chelated PVIm-Et delivered the highest amount of Zn2+ ions inside the cell, corresponding to the highest gene transfection, resulting in the remains of insulin in the conditioned medium. Therefore, the pDNA complex with Zn2+-chelated PVIm-Et has succeeded in the suppression of the insulin degradation by human hepatoma HepG2 cells. These results are expected to establish the new concept of the remote control of insulin concentration in blood for new diabetes therapy.

Report

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

    (23 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 2 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] By-Product-Free Intact Modification of Insulin by Cholesterol End-Modified Poly(ethylene glycol) for In Vivo Protein Delivery2018

    • Author(s)
      S. Asayama,* K. Nagashima, Y. Negishi, H. Kawakami
    • Journal Title

      Bioconjugate Chemistry

      Volume: 29 Issue: 1 Pages: 67-73

    • DOI

      10.1021/acs.bioconjchem.7b00593

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure-Activity Relationship between Zn2+-Chelated Alkylated Poly(1-vinylimidazole) and Gene Transfection2017

    • Author(s)
      S. Asayama,* M. Sakata, H. Kawakami
    • Journal Title

      Journal of Inorganic Biochemistry

      Volume: 173 Pages: 120-125

    • DOI

      10.1016/j.jinorgbio.2017.05.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile Method of Protein PEGylation by a Mono-Ion Complex2017

    • Author(s)
      S. Asayama,* K. Nagashima, H. Kawakami
    • Journal Title

      ACS Omega

      Volume: 2 Issue: 5 Pages: 2382-2386

    • DOI

      10.1021/acsomega.7b00462

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactoferrin-Modified Nanoparticles Loaded with Potent Antioxidant Mn-Porphyrins Exhibit Enhanced Antioxidative Activity In Vitro Intranasal Brain Delivery Model2017

    • Author(s)
      M. Matsuho, R. Kubota, S. Asayama, H. Kawakami
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 5 Issue: 9 Pages: 1765-1771

    • DOI

      10.1039/c6tb02599d

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] インスリン/コレステロール末端修飾PEG複合体による血糖降下作用2018

    • Author(s)
      朝山章一郎,長嶋果南,根岸洋一,川上浩良
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病治療を目指したZn2+/pDNA共送達システムのインスリン肝クリアランス抑制評価2017

    • Author(s)
      朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター、東北大学 (宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 持続的遺伝子発現型pDNA/PEGモノイオンコンプレックスの分子設計2017

    • Author(s)
      朝山章一郎,種市さくら,根岸洋一,川上浩良
    • Organizer
      遺伝子・デリバリー研究会第17回シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] pDNA/PEGモノイオンコンプレックスの機能向上とオリゴイオンコンプレックスの形成2017

    • Author(s)
      朝山章一郎,種市さくら,根岸洋一,川上浩良
    • Organizer
      第66回高分子学会年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Zn2+/pDNA共送達システムのインスリン肝クリアランス抑制機構解析2017

    • Author(s)
      朝山章一郎,永倉大賀,坂田瑞希,川上浩良
    • Organizer
      第66回高分子学会年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] インスリンの非共有結合PEGylation:コレステロール末端修飾PEGとインスリンの複合体形成2017

    • Author(s)
      朝山章一郎,長嶋果南,根岸洋一,川上浩良
    • Organizer
      第33回日本DDS学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Design of Mono-Ion Complex for In Vivo Diffusive Plasmid DNA Delivery2017

    • Author(s)
      Shoichiro Asayama, Atsushi Nohara, Sakura Taneichi, Yoichi Negishi, Hiroyoshi Kawakami
    • Organizer
      44th Annual Meeting & Exposition of the Controlled Release Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] モノイオンコンプレックスによるタンパク質の非共有結合PEGylation2017

    • Author(s)
      朝山章一郎,長嶋果南,川上浩良
    • Organizer
      第46回医用高分子シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] プロテインモノイオンコンプレックスによるカタラーゼのPEGylation効果2017

    • Author(s)
      朝山章一郎,長嶋果南,川上浩良
    • Organizer
      第66回高分子討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Biocompatible Highly Condensed Plasmid DNA for In Vivo Diffusive Delivery2017

    • Author(s)
      Shoichiro Asayama, Atsushi Nohara, Sakura Taneichi, Yoichi Negishi, Hiroyoshi Kawakami
    • Organizer
      The 25th Anniversary Congress of the European Society of Gene & Cell Therapy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コレステロール末端修飾PEGによるインスリンの非共有結合PEGylation2017

    • Author(s)
      朝山章一郎,長嶋果南,根岸洋一,川上浩良
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Zn2+/pDNA共送達システムのインスリン肝クリアランス抑制に基づく糖尿病治療への展開2016

    • Author(s)
      朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      日本バイオマテリアル学会シンポジウム2016
    • Place of Presentation
      福岡国際会議場 (福岡県福岡市)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Research-status Report
  • [Presentation] Zn2+/pDNA共送達システムによるインスリンの肝クリアランス抑制と糖尿病治療への展開2016

    • Author(s)
      朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      第65回高分子討論会
    • Place of Presentation
      神奈川大学 (神奈川県横浜市)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Zn2+/pDNA共送達システムによる細胞増殖促進2016

    • Author(s)
      永倉大賀、朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      第65回高分子討論会
    • Place of Presentation
      神奈川大学 (神奈川県横浜市)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Zn2+/プラスミドDNA共送達システムによる糖尿病治療へのアプローチ2016

    • Author(s)
      朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      第45回医用高分子シンポジウム
    • Place of Presentation
      産業技術総合研究所(東京都江東区)
    • Year and Date
      2016-07-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Zn2+/プラスミドDNA共送達システムによるインスリンの肝クリアランス抑制2016

    • Author(s)
      朝山章一郎、坂田瑞希、川上浩良
    • Organizer
      第32回日本DDS学術集会
    • Place of Presentation
      静岡県コンベンションアーツセンター (静岡県静岡市)
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
  • [Book] 生体分子化学 基礎から応用まで2017

    • Author(s)
      杉本直己,内藤昌信,橋詰峰雄,高橋俊太郎,田中直毅,建石寿枝,遠藤玉美樹,津本浩平,長門石曉,松原輝彦,上田実,朝山章一郎
    • Total Pages
      292
    • Publisher
      講談社
    • ISBN
      9784061568068
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 表面処理剤2018

    • Inventor(s)
      朝山章一郎
    • Industrial Property Rights Holder
      朝山章一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-010232
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] タンパク質吸着抑制表面処理剤2017

    • Inventor(s)
      朝山章一郎
    • Industrial Property Rights Holder
      朝山章一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-013942
    • Filing Date
      2017-01-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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