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Fundamental Research of Disease Imaging Taking Advantage of The Thermo-Responsive Molecules

Research Project

Project/Area Number 19K07016
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionShowa Pharmaceutical University

Principal Investigator

KARASAWA SATORU  昭和薬科大学, 薬学部, 教授 (80315100)

Co-Investigator(Kenkyū-buntansha) 渕 靖史  徳島文理大学, 薬学部, 助教 (40748795)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsナノ微粒子 / MRI造影剤 / 蛍光 / 温度応答性 / エチレングリコール / MRI / がん検出 / 自己集合化分子 / 蛍光イメージング / ガドリニウム / 自己集合体 / 温度応答 / がん
Outline of Research at the Start

がんと正常組織との間には様々な違いがある。例えばがん組織は、正常組織よりも高温である。我々は、高温で自己集合化しサイズアップする温度応答性分子に蛍光団を取り付け、がんへ微粒子が集積することを蛍光イメージングで確かめた。しかしながら、身体の深部まで撮像できない問題点があった。そこで今回、深部透過性が高い長波長発光とMRによるイメージングが可能な温度応答性プローブの開発を目的とする。

Outline of Final Research Achievements

Thermal-responsive nanoparticles(TRNP) are of great significant because the TRNPs were expected to accumulate into tumors by controlling the temperature. Three NPs consisted of Gadolinium (Gd-NPs), radical(RA-NPs), and fluorophore (FL-NPs) were designed and their morphologies, sizes, and physical properties were investigated. The Gd-NPs function as MRI contrast agent and the resulting contrast ability was much larger than those of commercial available agents. In the case of RA-NPs, the spherical NPs with ~ 30 nm were observed by a transmission electron microscopy (TEM). In contrast, the FL-NPs exhibited intensive emission, and the presence of spaces in NPs was observed by TEM images. Accordingly, taking advantage of the spaces, the FL-NPs allows to contain the anti-cancer agents into the spaces.

Academic Significance and Societal Importance of the Research Achievements

早期にがんを見つけること、がん細胞、がん組織を死滅させることは我々人類の願いである。本研究は、がんの高温性を利用したがんイメージングの研究であり、ナノ微粒子を使ってMRIや蛍光によるがん検出・診断を目的としている。MRI用の検出プローブでは、ナノ微粒子化することで高い造影効果が見出された。蛍光プローブでは、ナノ微粒子が中空であることを見出し、今後は中空の中に抗がん剤を導入することを予定している。本研究成果で得られたナノ微粒子型検出プローブは、早期がん検出・がん死滅に対して有効性が高いことが示唆された。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (36 results)

All 2022 2021 2020 2019 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 2 results) Presentation (17 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Effect of Alkynyl Group on Reactivity in Photoaffinity Labeling with 2‐Thienyl‐Substituted α‐Ketoamide2022

    • Author(s)
      Moriyama Takahiro、Mizukami Daiki、Yoritate Makoto、Usui Kazuteru、Takahashi Daisuke、Ota Eisuke、Sodeoka Mikiko、Ueda Tadashi、Karasawa Satoru、Hirai Go
    • Journal Title

      Chemistry A European Journal

      Volume: 28 Issue: 11 Pages: 1-5

    • DOI

      10.1002/chem.202103925

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Reversible Acid-Base Detection Reagents Based on Push-pull Type Aminonaphthyridine and Aminoquinoline Derivatives.2022

    • Author(s)
      S. Matsumoto, T. Umeno, K. Usui, S. Karasawa
    • Journal Title

      Bunseki Kagaku

      Volume: 71 Pages: 119-131

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] π‐Extended Push‐Pull‐Type Bicyclic Fluorophores Based on Quinoline and Naphthyridine Frameworks with an Iminophosphorane Fragment2021

    • Author(s)
      Umeno Tomohiro、Usui Kazuteru、Karasawa Satoru
    • Journal Title

      Asian Journal of Organic Chemistry

      Volume: - Issue: 5 Pages: 1123-1130

    • DOI

      10.1002/ajoc.202100015

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-<i>Z</i>′ Crystal Structure of Tricyclic Imidazonaphthyridine Derivatives and the Thermal Profiles of Their Polymorphs2021

    • Author(s)
      Matsumoto Shota、Umeno Tomohiro、Usui Kazuteru、Karasawa Satoru
    • Journal Title

      Crystal Growth & Design

      Volume: 21 Issue: 9 Pages: 5251-5260

    • DOI

      10.1021/acs.cgd.1c00585

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Artificial Host Molecules to Covalently Capture 8-Nitro-cGMP in Neutral Aqueous Solutions and in Cells2021

    • Author(s)
      Y. Fuchi, H. Murase, R. Kai, K. Kurata, S. Karasawa, and S. Sasaki*
    • Journal Title

      Bioconjugate Chem

      Volume: 32 Issue: 2 Pages: 385-393

    • DOI

      10.1021/acs.bioconjchem.1c00012

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] PushーPull Bisnaphthyridylamine Supramolecular Nanoparticles: Polarity‐Induced Aggregation and Crystallization‐Induced Emission Enhancement and Fluorescence Resonance Energy Transfer2021

    • Author(s)
      R. Hagihara, T. Umeno, S. Ueki, D. Yoshihara, Y. Fuchi, K, Usui, M. Sakuma, and Satoru Karasawa,*
    • Journal Title

      Chem Eur J

      Volume: 27 Issue: 9 Pages: 3039-3046

    • DOI

      10.1002/chem.202003854

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A fully synthetic 6-aza-artemisinin bearing an amphiphilic chain generates aggregates and exhibits anti-cancer activities2020

    • Author(s)
      H. Koi, N. Takahashi, Y. Fuchi, T. Umeno, Y. Muramatsu, H. Seimiya, Satoru Karasawa*, and H. Oguri*
    • Journal Title

      Org. Biomol.Chem

      Volume: 18 Issue: 28 Pages: 5339-5343

    • DOI

      10.1039/d0ob00919a

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization and Water-Proton Longitudinal Relaxivities of Liposome-Type Radical Nanoparticles Prepared via a Supramolecular Approach2020

    • Author(s)
      R. Shiraishi, S. Matsumoto, Y. Fuchi, T. Naganuma, D. Yoshihara, K. Usui, K. Yamada, and Satoru Karasawa*
    • Journal Title

      Langmuir

      Volume: 36 Issue: 19 Pages: 5280-5286

    • DOI

      10.1021/acs.langmuir.0c00610

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Push-Pull-Type Benzo[X]quinoline Derivatives (X = g or f): Environmentally Responsive Fluorescent Dyes with Multiple Functions2020

    • Author(s)
      Y. Fuchi, T. Umeno, Y. Abe, K. Ikeno, R. Yamasaki, I. Okamoto, K. Usui, and Satoru Karasawa
    • Journal Title

      J. Org. Chem.

      Volume: 85 Issue: 20 Pages: 13177-13190

    • DOI

      10.1021/acs.joc.0c01878

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Substituents on the Properties of Metal-Free MRI Contrast Agents2019

    • Author(s)
      Shiraishi Ryoma、Kaneko Tomoyo、Usui Kazuteru、Naganuma Tatsuya、Iizuka Naoko、Morishita Kosuke、Kobayashi Shigeki、Fuchi Yasufumi、Matsuoka Yuta、Hirai Go、Yamada Ken-ichi、Karasawa Satoru
    • Journal Title

      ACS Omega

      Volume: 4 Issue: 24 Pages: 20715-20723

    • DOI

      10.1021/acsomega.9b03003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Turn-On Probes for Acids Triggered by Aromaticity Enhancement Using Tricyclic Amidine Derivatives2019

    • Author(s)
      Matsumoto Shota、Fuchi Yasufumi、Usui Kazuteru、Hirai Go、Karasawa Satoru
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 84 Issue: 11 Pages: 6612-6622

    • DOI

      10.1021/acs.joc.9b00023

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Selective synthesis of substituted amino-quinoline derivatives by C-H activation and fluorescence evaluation of their lipophilicity-responsive properties2019

    • Author(s)
      Fuchi Yasufumi、Sakuma Masaomi、Ohyama Kohei、Hagihara Ryusuke、Kohno Minaki、Hamada Koichi、Mizutani Akihiro、Karasawa Satoru
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 17723-17723

    • DOI

      10.1038/s41598-019-53882-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photophysical Properties of Emissive Pyrido[3,2‐c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus2019

    • Author(s)
      Sakuma Masaomi、Fuchi Yasufumi、Usui Kazuteru、Karasawa Satoru
    • Journal Title

      Chemistry An Asian Journal

      Volume: 14 Issue: 21 Pages: 3938-3945

    • DOI

      10.1002/asia.201901200

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fluorescence Properties and Exciplex Formation of Emissive Naphthyridine Derivatives: Application as Sensors for Amines2019

    • Author(s)
      Hirota Junko、Usui Kazuteru、Fuchi Yasufumi、Sakuma Masaomi、Matsumoto Shota、Hagihara Ryusuke、Karasawa Satoru
    • Journal Title

      Chemistry A European Journal

      Volume: 25 Issue: 65 Pages: 14943-14952

    • DOI

      10.1002/chem.201903643

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] アルミニウムイオン選択的ターンオン型蛍光プローブの開発2022

    • Author(s)
      松本 祥汰、梅野 智大、臼井 一晃、川幡 正俊、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ペプチド固相合成のための定量的なアミノ基検出法の開発2022

    • Author(s)
      藤原 萌圭、梅野 智大、臼井 一晃、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 塩基性蛍光分子によるメタノール選択的蛍光検出法の開発2022

    • Author(s)
      梅野 智大、瀬戸 玲美、松本 祥汰、臼井 一晃、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] イオン性アクリジン誘導体の合成と物性解析2022

    • Author(s)
      奥山 泰成、畑 督、松本 祥汰、梅野 智大、臼井 一晃、渕 靖史、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 螺旋構造内部置換型ヘリセンのキラル光学特性2022

    • Author(s)
      臼井 一晃、江藤 亮介、成田 望実、横尾 淳、山本 耕介、井川 和宣、友岡 克彦、今井 喜胤、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ピリダジン環を含むヘリセン誘導体の合成、構造と光物性2022

    • Author(s)
      笹屋 美歩、臼井 一晃、天野 亜美、村瀬 早槻、松本 祥汰、梅野 智大、濵田 浩一、水谷 顕洋、唐澤 悟
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] イミダゾナフチリジンから骨格から成る蛍光プローブの開発2021

    • Author(s)
      松本祥汰・梅野智大・臼井一晃・唐澤悟
    • Organizer
      第33回バイオメディカル分析科学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] グアニジノ基を有する蛍光分子によるメタノール選択的蛍光検出法の開発2021

    • Author(s)
      梅野智大・瀬戸玲美・臼井一晃・唐澤悟
    • Organizer
      第33回バイオメディカル分析科学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] カーブ構造を有するイミダゾナフチリジン誘導体の加熱結晶相転移2021

    • Author(s)
      松本祥汰・梅野智大・臼井一晃・唐澤悟
    • Organizer
      第31回基礎有機化学討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] D-A 型アミン検出試薬の開発とペプチド固相合成への応用2021

    • Author(s)
      梅野智大・臼井一晃・唐澤悟
    • Organizer
      第31回基礎有機化学討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ペプチド固相合成のための新規アミノ基検出法の開発研究2021

    • Author(s)
      梅野智大、臼井一晃、唐澤悟
    • Organizer
      日本薬学会 第141回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ジヒドロピリダジン環を含むアザ[5]ヘリセンの合成と物性評価2021

    • Author(s)
      梅野智大、臼井一晃、唐澤悟
    • Organizer
      日本薬学会 第141回年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Fluorescence properties of push-pull type benzoquinoline derivatives2019

    • Author(s)
      Yasufumi Fuchi・Satoru Karasawa
    • Organizer
      27th International Society of Heterocyclic Chemistry Congress
    • Related Report
      2019 Research-status Report
  • [Presentation] 三環性プッシュ―プル型新規蛍光分子の合成と物性評価2019

    • Author(s)
      渕 靖史・池野 敬太・臼井 一晃・唐澤 悟
    • Organizer
      第13回有機π電子系シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 8-チオグアノシンを標的としたturn-on型蛍光プローブの創製2019

    • Author(s)
      倉田 翔・渕 靖史・甲斐 亮補・佐々木 茂貴・唐澤 悟
    • Organizer
      第17回ホスト―ゲスト・超分子化学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 新規N含有三環性蛍光団の合成と蛍光特性評価2019

    • Author(s)
      池野 敬太・渕 靖史・臼井 一晃・唐澤 悟
    • Organizer
      第30回基礎有機化学討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 芳香族性が制御された三環性アミジン誘導体の合成と蛍光特性2019

    • Author(s)
      松本祥汰・臼井一晃・渕靖史・唐澤 悟
    • Organizer
      第30回基礎有機化学討論会
    • Related Report
      2019 Research-status Report
  • [Book] Molecular Technology Volume2 (Edited by H. Yamamoto and T. Kato)2019

    • Author(s)
      Satoru Karasawa
    • Total Pages
      8
    • Publisher
      Wiley-VCH
    • ISBN
      9783527820450
    • Related Report
      2019 Research-status Report
  • [Remarks]

    • URL

      https://www.shoyaku.ac.jp/research/laboratory/bunseki

    • Related Report
      2020 Research-status Report
  • [Remarks] 昭和薬科大学ホームページ

    • URL

      https://www.shoyaku.ac.jp/research/laboratory/bunseki/top

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] アミン類検出薬2021

    • Inventor(s)
      唐澤悟・梅野智大・松本祥汰・臼井一晃
    • Industrial Property Rights Holder
      唐澤悟・梅野智大・松本祥汰・臼井一晃
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-033419
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 新規化合物及び該化合物を含む脂肪滴検出用試薬2019

    • Inventor(s)
      唐澤 悟、渕 靖史、大山耕平、佐久間雅臣 他3名
    • Industrial Property Rights Holder
      唐澤 悟、渕 靖史、大山耕平、佐久間雅臣 他3名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-090840
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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