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Development of multicolor and multifunctional fluorescent probes for single-cell detection of cancer

Research Project

Project/Area Number 19H02826
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Kamiya Mako  東京大学, 大学院医学系研究科(医学部), 准教授 (90596462)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords蛍光プローブ / がんイメージング / がん検出 / 光機能性分子 / がん / 酵素活性 / がん細胞
Outline of Research at the Start

血液中循環がん細胞(CTC)の解析は、がんの進行や治療効果の判定などを非侵襲的に観察する検査法として期待されている。本研究では、各々のがん細胞が固有の酵素の活性パターンを有することに着目し、種々の酵素活性を可視化する多色・多機能な蛍光プローブ群の開発することで、異なる細胞種が混在する中からがん細胞をシングルセルレベルで検出するための技術を開発することを目指す。

Outline of Final Research Achievements

To develop multicolor and multifunctional fluorescent probes for visualizing the characteristic pattern of enzyme activity of cancer cells at the single-cell resolution, we have extended our previously established molecular design strategy. As a result, we developed (1) Activatable photosensitizers that specifically induce cell death in cells expressing the target enzymes, (2) Fluorescent probes with improved cellular retention targeting peptidases that are overexpressed in cancer for durable tumor imaging, and also compared (3) intracellular retention of quinone methide or azaquinone methide intermediates by developing new caged fluorophores. Based on these findings, we expect to establish a new method for detecting and analyzing cancer with improved sensitivity and specificity.

Academic Significance and Societal Importance of the Research Achievements

血液中循環がん細胞(circulating tumor cells、CTC)の解析は、がんの進行や治療効果を非侵襲的にモニタリングするために有効と期待されている。そのため、本研究で得られた知見を活用して、がん細胞が有する特徴的な“酵素活性パターン”をシングルセルレベルで可視化する多色・多機能な有機小分子蛍光プローブ群を開発することができれば、異なる細胞種が混在する中からCTCなどのがん細胞をシングルセルレベルで検出する技術の開発につながると期待される。このような技術は、がんの早期発見・早期治療、進行度の特定・治療効果の判定、ひいては今後の個別化医療の発展にも貢献すると期待される。

Report

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

    (31 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 8 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Rapid visualization of deeply located tumors in vivo by intravenous administration of a γ-glutamyltranspeptidase-activated fluorescent probe2022

    • Author(s)
      Akihiro Nakada, Takuma Maruyama, Mako Kamiya, Kenjiro Hanaoka, Yasuteru Urano
    • Journal Title

      Bioconjugate Chemistry

      Volume: 33 Issue: 3 Pages: 523-529

    • DOI

      10.1021/acs.bioconjchem.2c00039

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular probes for fluorescence image-guided cancer surgery2022

    • Author(s)
      Ito Ren、Kamiya Mako、Urano Yasuteru
    • Journal Title

      Current Opinion in Chemical Biology

      Volume: 67 Pages: 102112-102112

    • DOI

      10.1016/j.cbpa.2021.102112

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a fluorescent probe library enabling efficient screening of tumour-imaging probes based on discovery of biomarker enzymatic activities2022

    • Author(s)
      Kuriki Yugo、Yoshioka Takafusa、Kamiya Mako、Komatsu Toru、Takamaru Hiroyuki、Fujita Kyohhei、Iwaki Hirohisa、Nanjo Aika、Akagi Yuki、Takeshita Kohei、Hino Haruaki、Hino Rumi、Kojima Ryosuke、Ueno Tasuku、Hanaoka Kenjiro、Abe Seiichiro、Saito Yutaka、Nakajima Jun、Urano Yasuteru
    • Journal Title

      Chemical Science

      Volume: 13 Issue: 16 Pages: 4474-4481

    • DOI

      10.1039/d1sc06889j

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid fluorescence imaging of human hepatocellular carcinoma using the β-galactosidase-activatable fluorescence probe SPiDER-βGal2021

    • Author(s)
      Ogawa Soichiro、Kubo Hidemasa、Murayama Yasutoshi、Kubota Takeshi、Yubakami Masayuki、Matsumoto Tatsuya、Yamamoto Yusuke、Morimura Ryo、Ikoma Hisashi、Okamoto Kazuma、Kamiya Mako、Urano Yasuteru、Otsuji Eigo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 17946-17946

    • DOI

      10.1038/s41598-021-97073-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorescence Imaging Using Enzyme-Activatable Probes for Real-Time Identification of Pancreatic Cancer2021

    • Author(s)
      Takahashi Ryugen、Ishizawa Takeaki、Sato Masumitsu、Inagaki Yoshinori、Takanka Mariko、Kuriki Yugo、Kamiya Mako、Ushiku Tetsuo、Urano Yasuteru、Hasegawa Kiyoshi
    • Journal Title

      Frontiers in Oncology

      Volume: 11 Pages: 714527-714527

    • DOI

      10.3389/fonc.2021.714527

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Topical Fluorescent Probe for Detection of Glioblastoma2021

    • Author(s)
      Kitagawa Yosuke、Tanaka Shota、Kamiya Mako、Kuriki Yugo、Yamamoto Kyoko、Shimizu Takenori、Nejo Takahide、Hana Taijun、Matsuura Reiko、Koike Tsukasa、Yamazawa Erika、Kushihara Yoshihiro、Takahashi Satoshi、Nomura Masashi、Takami Hirokazu、Takayanagi Shunsaku、Mukasa Akitake、Urano Yasuteru、Saito Nobuhito
    • Journal Title

      Clinical Cancer Research

      Volume: 27 Issue: 14 Pages: 3936-3947

    • DOI

      10.1158/1078-0432.ccr-20-4518

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-Galactosidase is a target enzyme for detecting peritoneal metastasis of gastric cancer2021

    • Author(s)
      Kubo Hidemasa、Murayama Yasutoshi、Ogawa Soichiro、Matsumoto Tatsuya、Yubakami Masayuki、Ohashi Takuma、Kubota Takeshi、Okamoto Kazuma、Kamiya Mako、Urano Yasuteru、Otsuji Eigo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 10664-10664

    • DOI

      10.1038/s41598-021-88982-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneously Blinking Fluorophores Based on Nucleophilic Addition/Dissociation of Intracellular Glutathione for Live-Cell Super-resolution Imaging2020

    • Author(s)
      Morozumi Akihiko、Kamiya Mako、Uno Shin-nosuke、Umezawa Keitaro、Kojima Ryosuke、Yoshihara Toshitada、Tobita Seiji、Urano Yasuteru
    • Journal Title

      Journal of the American Chemical Society

      Volume: - Pages: 9625-9633

    • DOI

      10.1021/jacs.0c00451

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] γ‐Glutamyltranspeptidase (GGT)‐Activatable Fluorescence Probe for Durable Tumor Imaging2020

    • Author(s)
      Obara Rui、Kamiya Mako、Tanaka Yoko、Abe Atsuki、Kojima Ryosuke、Kawaguchi Tokuichi、Sugawara Minoru、Takahashi Akiko、Noda Tetsuo、Urano Yasuteru
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 60 Issue: 4 Pages: 2125-2129

    • DOI

      10.1002/anie.202013265

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and Accurate Visualization of Breast Tumors with a Fluorescent Probe Targeting α-Mannosidase 2C12020

    • Author(s)
      Fujita Kyohhei、Kamiya Mako、Yoshioka Takafusa、Ogasawara Akira、Hino Rumi、Kojima Ryosuke、Ueo Hiroaki、Urano Yasuteru
    • Journal Title

      ACS Central Science

      Volume: 6 Issue: 12 Pages: 2217-2227

    • DOI

      10.1021/acscentsci.0c01189

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activatable Photosensitizer for Targeted Ablation of lacZ-Positive Cells with Single-Cell Resolution2019

    • Author(s)
      Chiba Mayumi、Kamiya Mako、Tsuda-Sakurai Kayoko、Fujisawa Yuya、Kosakamoto Hina、Kojima Ryosuke、Miura Masayuki、Urano Yasuteru
    • Journal Title

      ACS Central Science

      Volume: 5 Issue: 10 Pages: 1676-1681

    • DOI

      10.1021/acscentsci.9b00678

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Click反応を利用したLAT1発現がん細胞の蛍光イメージング技術の開発2022

    • Author(s)
      伊藤廉、神谷真子、浦野泰照
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ProTide chemistryに基づく 新規カルボキシペプチダーゼ活性検出プローブの開発2022

    • Author(s)
      曽川マリー、栗木優五、神谷真子、浦野泰照
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アミノペプチダーゼ活性を標的とした新規がん高集積型SPECTプローブの開発2022

    • Author(s)
      阿部篤生、神谷真子、大貫和信、藤井博史、浦野泰照
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] オリジナル化学プロープの開発による迅速がん蛍光検出2021

    • Author(s)
      神谷真子
    • Organizer
      新規素材探索研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] オリジナル化学プローブの創製による 生体分子イメージング2021

    • Author(s)
      神谷真子
    • Organizer
      第23回発動分子科学セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Chemical probes for cancer-associated enzymes for fluorescence imaging of cancer2021

    • Author(s)
      Mako Kamiya, Yasuteru Urano
    • Organizer
      Pacifichem2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identifications and Utilization of Biomarker Glycosidases for Rapid and Clinical Fluorescence Imaging of Breast and Lung Cancer2021

    • Author(s)
      藤田恭平、神谷真子、中島淳、上尾裕昭、浦野泰照
    • Organizer
      第15回 日本分子イメージング学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification and Utilization of Biomarker Glycosidases for Rapid and Sensitive Fluorescence Detection of Breast and Lung Cancer2021

    • Author(s)
      藤田恭平、神谷真子、中島淳、上尾裕昭、浦野泰照
    • Organizer
      日本ケミカルバイオロジー学会 第15回年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification and utilization of a-mannosidase 2C1 as a biomarker enzyme for rapid and clinical fluorescence imaging of breast tumors2021

    • Author(s)
      藤田恭平、神谷真子、上尾裕明、浦野泰照
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Hexosaminidaseを標的とした細胞内滞留型がん蛍光イメージングプローブの開発2021

    • Author(s)
      竹下航平、神谷真子、浦野泰照
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん蛍光イメージングに資するLAT1蛍光基質の開発2021

    • Author(s)
      伊藤廉、神谷真子、浦野泰照
    • Organizer
      日本薬学会 第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 化学プローブを精密にデザインして 癌を光らせる!2020

    • Author(s)
      神谷 真子
    • Organizer
      日本学術会議第三部主催 公開シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Spontaneously blinking fluorophores for live-cell super-resolution imaging2020

    • Author(s)
      神谷 真子
    • Organizer
      EMBL Chemical Biology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Rapid cancer imaging by activable fluorescence probes for exopeptidases2020

    • Author(s)
      神谷 真子
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] LacZ発現細胞の特異的蛍光検出および細胞死誘導を可能とするケミカルプローブの開発2020

    • Author(s)
      神谷 真子、浦野 泰照
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Chemical probes for fluorescence imaging or ablation of lacZ-positive cells with single cell resolution2019

    • Author(s)
      Mako Kamiya, Yasuteru Urano
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] がん細胞の蛍光イメージング技術2022

    • Inventor(s)
      浦野泰照、神谷真子、伊藤廉、藤田恭平
    • Industrial Property Rights Holder
      国立大学法人 東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-032958
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] カルボキシペプチダーゼ検出赤色蛍光プローブ2021

    • Inventor(s)
      浦野泰照、神谷真子、曽川マリー、久米春喜、山田大介
    • Industrial Property Rights Holder
      国立大学法人 東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] LAT1基質となる蛍光プローブ2021

    • Inventor(s)
      浦野 泰照,神谷 真子,伊藤 廉
    • Industrial Property Rights Holder
      国立大学法人東 京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas

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

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