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Development of an in vivo measurement system based on NV center-integrated nanodiamonds

Research Project

Project/Area Number 23K21857
Project/Area Number (Other) 21H03832 (2021-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2021-2023)
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Osada Kensuke  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 分子イメージング診断治療研究部, グループリーダー (10396947)

Co-Investigator(Kenkyū-buntansha) 阿部 浩之  国立研究開発法人量子科学技術研究開発機構, 高崎量子応用研究所 量子機能創製研究センター, 主任研究員 (30354947)
Project Period (FY) 2021-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2024: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
KeywordsPEG化 / ステルス化 / 重なり合い濃度 / 高分子付加 / ナノ量子センサー / ナノダイヤモンド / NVセンター / ナノセンサー
Outline of Research at the Start

ダイヤモンドの窒素-空孔(NV)センターは、周囲の物理的・化学的環境を探知できる量子センサーである。本研究では、ナノメートルサイズのダイヤモンド(ND)に対し、電子線加速機を使ってNVセンターを多数造り込むことと、生体適合性高分子で表面修飾し、ステルス性を付与する方法論の開発を行う。これによって、細胞や体の中で執り行われている化学反応を計測することを可能とする生体ナノ量子センサーシステムを創出することを目的とする。

Outline of Final Research Achievements

For nanodiamonds (NDs) with a particle size of 50 nm, we optimized the electron beam irradiation dose, heat treatment temperature and duration, and successfully obtained NDs with significantly enhanced fluorescence intensity derived from NV(-) centers. In parallel, we developed methods of PEGylation and a quantitative analysis based on the overlapping concentration of adjacent PEG chains as a parameter (applied for patent No. 2023-139263). Specifically, PEG molecules with molecular weights ranging from 2 kDa to 40 kDa were grafted onto the ND, and the interrelationship among PEG molecular weight, PEG overlapping concentration, and protein adsorption suppression effect were clarified. The PEGylated NDs demonstrated a significant reduction in lung adsorption. These studies were reported in a peer-reviewed article (Langmuir, 2024).

Academic Significance and Societal Importance of the Research Achievements

本研究によって、最も汎用的なPEG修飾法で到達可能な最大密度のPEG化NDの作成法が示されるとともに、重なり合い濃度の定量法の開発によって、NDを含む「堅い」ナノ粒子に全般に対する高分子修飾に明確な物理化学的描像を与える事が可能となった。また、NVセンターの増設技術と、PEG化によって血中投与後の肺吸着が大幅に抑制されたことで、個体への全身投与によるin vivo計測の実現可能性が示された。今後、細胞や体の中の化学反応を計測することで生命活動の作動原理を熱力学で理解する学術への進展が期待され、生命科学の飛躍的発展とその知見を基にした創薬と医療の発展が期待される。

Report

(4 results)
  • 2024 Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (53 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (5 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (34 results) (of which Int'l Joint Research: 13 results,  Invited: 21 results) Book (3 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] ミシガン大学/オハイオ州立大学(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] マインツ大学(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ライデン大学(オランダ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] ミシガン大学/オハイオ州立大学(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] マインツ大学(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Block copolymer-stabilized MOF hybrids loading Pd nanoparticles enable tumor remission through near-infrared photothermal therapy2024

    • Author(s)
      Shang-Wei Li, Ming-Feng Hsieh, Taehun Hong, Pengwen Chen, Kensuke Osada, Xueying Liu, Ichio Aoki, Jiashing Yu, Kevin C.-W. Wu, Horacio Cabral
    • Journal Title

      Advanced NanoBiomed Research

      Volume: - Issue: 1

    • DOI

      10.1002/anbr.202470011

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantification of poly(ethylene glycol) crowding on nanodiamonds toward quantum biosensor for improved prevention effects on protein adsorption and lung accumulation2024

    • Author(s)
      K. Rikiyama, N. Maehara, H. Abe, Y. Nishimura, H. Yukawa, K. Kaminaga, R. Igarashi, K. Osada
    • Journal Title

      Langmuir

      Volume: - Issue: 18 Pages: 94719480-94719480

    • DOI

      10.1021/acs.langmuir.3c03988

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-Folding Macromolecular Drug Carrier for Cancer Imaging and Therapy2023

    • Author(s)
      S. Gao, Y. Miura, A. Sumiyoshi, S. Ohno, K. Ogata, T. Nomoto, M. Matsui, Y. Honda, M. Suzuki, M. Iiyama, K. Osada, I. Aoki, N. Nishiyama
    • Journal Title

      Advanced Science

      Volume: 11 Issue: 7 Pages: 2304171-2304171

    • DOI

      10.1002/advs.202304171

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Size-tunable PEG-grafted copolymers as a polymeric nanoruler for passive targeting muscle tissues.2022

    • Author(s)
      M. Naito, Y. Watanuki, K. Toh, J. Yum, B. S. Kim, K. Taniwaki, S. Ogura, H. Ishida, M. Cho, H. Chaya, K. Miyajima, K. Osada, K. Minegishi, Y. Aoki, Y. Yamasaki, K. Miyata,
    • Journal Title

      Journal of Controlled Release

      Volume: 347 Pages: 607-614

    • DOI

      10.1016/j.jconrel.2022.05.030

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Delivery of aPD-L1 antibody to i.p. tumors via direct penetration by i.p. route: beyond EPR effect.2022

    • Author(s)
      M. Yamamoto, T. Kurino, R. Matsuda, H. S. Jones, Y. Nakamura, T. Kanamori, A. B. Tsuji, A. Sugyo, R. Tsuda, Y. Matsumoto, Y. Sakurai, H. Suzuki, M. Sano, K. Osada, T. Uehara, Y. Ishii, H. Akita, Y. Arano, A. Hisaka, H. Hatakeyama,
    • Journal Title

      Journal of Controlled Release

      Volume: 352 Pages: 328-337

    • DOI

      10.1016/j.jconrel.2022.10.032

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Size-controlled bimodal in vivo nanoprobes as near-infrared phosphors and positive contrast agents for magnetic resonance imaging2021

    • Author(s)
      K. Okubo, R. Takeda, S. Murayama, M. Umezawa, M. Kamimura, K. Osada, I. Aoki, K. Soga,
    • Journal Title

      Science and Technology of Advanced Materials

      Volume: 22 Issue: 6 Pages: 160-172

    • DOI

      10.3390/pharmaceutics13060800

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bridging mRNA and polycation using RNA oligonucleotide derivatives improves the robustness of polyplex micelle for efficient mRNA delivery.2021

    • Author(s)
      N. Yoshinaga, S. Uchida, A. Dirisala, M. Naito, K. Koji, K. Osada, H. Cabral, K. Kataoka,
    • Journal Title

      Advanced Healthcare Materials,

      Volume: - Issue: 9 Pages: 2102016-2102016

    • DOI

      10.1002/adhm.202102016

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Liver sinusoidal wall coating polymer to promote the efficacy of gene therapy drugs, The 40th International Conference of Photopolymer Science and Technology2023

    • Author(s)
      K. Osada
    • Organizer
      The 40th International Conference of Photopolymer Science and Technology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Polymeric Architectures to Perform Virus Functions and its Challenge to Pancreatic Cancer2023

    • Author(s)
      K. Osada
    • Organizer
      International Conference on Precision Nanomedicine in Theranostics & The 2023 Annual Meeting of Taiwan Nanomedicine Society
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ナノダイヤモンドの定量的PEG化2023

    • Author(s)
      長田健介
    • Organizer
      量子生命科学先端フォーラム2023夏の研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 生体量子センシングのためのナノダイヤモンドの定量的PEG化2023

    • Author(s)
      長田健介, 力山和晃
    • Organizer
      第72回高分子討論会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 日本学術振興会特別研究員応募書類作成で気をつけたいこと2023

    • Author(s)
      長田健介
    • Organizer
      NITech PGCプログラム日本学術振興会特別研究員申請支援セミナー
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 高分子で挑む膵臓がんの遺伝子/核酸治療2023

    • Author(s)
      長田健介
    • Organizer
      増殖制御遺伝子TOB研究会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Quantification of PEG crowding grafted onto nanodiamonds2023

    • Author(s)
      K. Osada
    • Organizer
      The 11th Conference on Exploring Next-Generation Materials Science and Nanoscience (11thCENG-MSN) and Workshop on Soft and Nano Materials Orchestrated with Wisdom from Japan 2024 (SNOWJ2024)
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nano-Ruler MRI contrast agent to detect inflammatory vasculature2023

    • Author(s)
      K. Osada, N. Maehara, A. Sumiyoshi, M. Naito, K. Miyata, I. Aoki,
    • Organizer
      The 11th Takeda Science Foundation Symposium on Pharmasciences, Congres Convention Center
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nano-Ruler MRI contrast agent to detect inflammatory vasculature2023

    • Author(s)
      K. Osada
    • Organizer
      MRI Symposium Osaka
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transient stealth coating of liver sinusoidal wall by PEG for retargeting nanomedicines2023

    • Author(s)
      K. Osada
    • Organizer
      1st Workshop on Soft and Nano Materials Orchestrated with Wisdom from Japan and Korea 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体量子センシングのためのナノダイヤモンドの定量的PEG化2023

    • Author(s)
      長田健介
    • Organizer
      第13回ナノバイオ若手ネットワーキングシンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] Polymers for cancer therapy and diagnosis2023

    • Author(s)
      K. Osada
    • Organizer
      Seminar in Division of BioTherapeutics, Leiden Univeristy
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Artificial viruses to target cancers by polymer nanoassembly technology2023

    • Author(s)
      長田健介
    • Organizer
      OIST Seminar
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 化学で生命に迫る ~高分子化学でがんに挑む2022

    • Author(s)
      長田健介
    • Organizer
      東進ハイスクール未来発見講座
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ナノダイヤモンドの定量的PEG化の試み2022

    • Author(s)
      長田健介
    • Organizer
      量子計測技術による細胞生物物理学の進展と生命のパラメトリク生理機能の解明への展開
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん微小環境を診る高分子造影剤の開発とPDXモデルへの適用2022

    • Author(s)
      長田健介, 力山和晃, 綿貫裕介, 内藤瑞, 宮田完二郎, 住吉晃, 青木伊知男
    • Organizer
      第38回日本DDS学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] がん微小環境を診る高分子造影剤の開発とPDXモデルへの適用2022

    • Author(s)
      長田健介
    • Organizer
      第71回高分子討論会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 高分子化学を道具にがんに挑戦する試みとナノダイヤモンド量子計測への展開2022

    • Author(s)
      長田健介
    • Organizer
      大阪大学蛋白研セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 高分子化学を道具にがんに挑戦する研究2022

    • Author(s)
      長田健介
    • Organizer
      茨城県立水戸第一高等学校大学模擬講義
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん微小環境を診る高分子造影剤の開発とPDXモデルへの適用2022

    • Author(s)
      長田健介, 力山和晃, 綿貫裕介, 内藤瑞, 宮田完二郎, 住吉晃, 青木伊知男
    • Organizer
      第44回バイオマテリアル学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] A safe liver sinusoidal wall coating agent to promote the efficacy of gene therapy drugs2022

    • Author(s)
      長田健介
    • Organizer
      International Symposium on Chemistry 2022 and the 2nd Kyutech-KKU International Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A safe liver sinusoidal wall coating agent to promote the efficacy of gene therapy drugs2022

    • Author(s)
      長田健介
    • Organizer
      The 5th International Conference on Nanospace Materials 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Through the stromal barrier to pancreatic cancer cell nests: Single-stranded DNA-packaged polyplex micelle as AAV-inspired compact gene vector2022

    • Author(s)
      長田健介
    • Organizer
      The 5th International Workshop by the 174th Committee on Coexistence of Biology and Nanodevices
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A safe liver sinusoidal wall coating agent to promote the efficacy of gene therapy drugs2022

    • Author(s)
      長田健介
    • Organizer
      The 4th International Conference on Materials Research and Innovation
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 化学で生命を作る挑戦2022

    • Author(s)
      長田健介
    • Organizer
      MRI Collaborator’s Workshop 2022
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ナノメディシンの送達効率を高める肝類洞内皮壁高分子コーティング剤2021

    • Author(s)
      長田健介, Anjaneyulu Dirisala, 内田智士, 片岡一則
    • Organizer
      第15回日本分子イメージング学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵臓がんの間質を超える一本鎖DNA内包ポリプレックスミセル2021

    • Author(s)
      長田健介, Theofilus A. Tockary, 片岡一則
    • Organizer
      第37回日本DDS学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高分子で作る人工ウイルスと遺伝子治療への展開2021

    • Author(s)
      長田健介
    • Organizer
      CSJ化学フェスタ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] DNAをたたむ、遺伝子を発現させる、病気を治す2021

    • Author(s)
      長田健介
    • Organizer
      茨城県立水戸第一高等学校大学模擬講義
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 非ウイルス性遺伝子治療 ~新しい遺伝子ベクターの設計と医療への応用~2021

    • Author(s)
      長田健介
    • Organizer
      BioJapan
    • Related Report
      2021 Annual Research Report
  • [Presentation] 核酸デリバリーシステムにおける核酸とポリアミノ酸との相互作用解析2021

    • Author(s)
      長田健介
    • Organizer
      BINDS NMR報告会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 生体計測を目指したナノダイヤモンド量子センサーの開発2021

    • Author(s)
      長田健介
    • Organizer
      スイゼンジノリ・サクラン研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ナノダイヤモンドを用いた生体ナノ量子センサーの開発2021

    • Author(s)
      長田健介
    • Organizer
      福岡工業大学総合研究機構エレクトロニクス研究所講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Single-stranded DNA-packaged Polyplex Micelle as AAV-inspired Compact Gene Vector to Systemically Target Stroma-rich Pancreatic Cancer2021

    • Author(s)
      長田健介
    • Organizer
      ICMARI2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] Drug Delivery System2022

    • Author(s)
      長田健介
    • Total Pages
      10
    • Publisher
      日本DDS学会
    • Related Report
      2021 Annual Research Report
  • [Book] 高分子2021

    • Author(s)
      長田健介
    • Total Pages
      2
    • Publisher
      高分子学会
    • Related Report
      2021 Annual Research Report
  • [Book] Drug Delivery System2021

    • Author(s)
      青木伊知男, 長田健介, 住吉晃, Bakalova Rumiana
    • Total Pages
      17
    • Publisher
      日本DDS学会
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 単一高分子からなる自己凝集型ミセル2023

    • Inventor(s)
      三浦裕,西山伸宏,ガオシャン,青木伊知男,長田健介,住吉晃,他
    • Industrial Property Rights Holder
      東京工業大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 修飾済基材,修飾済基材の製造方法,及び,修飾済基材における重なり合い密度の評価方法2023

    • Inventor(s)
      長田健介, 力山和晃
    • Industrial Property Rights Holder
      量子科学技術研究開発機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 単一高分子粒子、活性分子複合体、単一高分子粒子の製造方法、腫瘍サイズの計測方法、腫瘍内の微細構造の計測方法、生体組織のイメージング方法、ドラッグデリバリーシステム、造影剤キット2023

    • Inventor(s)
      長田健介, 力山和晃, 住吉晃, 青木伊知男, 内藤瑞, 等
    • Industrial Property Rights Holder
      長田健介, 力山和晃, 住吉晃, 青木伊知男, 内藤瑞, 等
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 単一高分子粒子、活性分子複合体、単一高分子粒子の製造方法、腫瘍サイズの計測方法、腫瘍内の微細構造の計測方法、生体組織のイメージング方法、ドラッグデリバリーシステム、造影剤キット2022

    • Inventor(s)
      長田健介, 力山和晃, 住吉晃, 青木伊知男, 内藤瑞, 等
    • Industrial Property Rights Holder
      長田健介, 力山和晃, 住吉晃, 青木伊知男, 内藤瑞, 等
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2021-04-28   Modified: 2026-01-16  

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