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Development of bioactive nanocarbon composite enabling spatial and temporal control of the metastatic bone cancer environment and biosafety assessments

Research Project

Project/Area Number 17H01584
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionShinshu University

Principal Investigator

Saito Naoto  信州大学, 学術研究院保健学系, 教授 (80283258)

Co-Investigator(Kenkyū-buntansha) 手嶋 勝弥  信州大学, 学術研究院工学系, 教授 (00402131)
中村 真紀  国立研究開発法人産業技術総合研究所, 材料・化学領域, 主任研究員 (00568925)
宇田川 信之  松本歯科大学, 歯学部, 教授 (70245801)
湯田坂 雅子  国立研究開発法人産業技術総合研究所, 材料・化学領域, 招聘研究員 (70159226)
佐藤 義倫  東北大学, 環境科学研究科, 准教授 (30374995)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2021: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2018: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2017: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Keywords癌骨転移 / 抗癌剤 / 抗破骨細胞薬 / カーボンファイバー / カーボンナノホーン / Drug delivery system / 骨軟部腫瘍 / 癌の骨転移 / DDS / 骨・軟部腫瘍学 / 癌転移骨
Outline of Final Research Achievements

We have demonstrated that composites of carbon nanohorns and bisphosphonate drugs could be phagocytosed into osteoclasts to significantly inhibit their bone resorptive function. In addition, carbon fiber and anticancer drug composites were observed to effectively reduce cancer cell number in both in vitro and in vivo studies. The carbon fiber also acted as osseous scaffolding and promoted bone tissue regeneration. Thus, when introducing carbon materials complexed to bioactive molecules into metastatic bone for interactions with osteoclasts, cancer cells, and osteoblasts, the metastatic bone environment can be controlled spatially as well as temporally by a series of responses, namely, bone destruction termination, cancer cell suppression, and bone repair promotion.

Academic Significance and Societal Importance of the Research Achievements

カーボンナノホーンとビスホスホネートは破骨細胞を抑制したが、この材料と薬を連結させるHAそのものが骨基質の成分であり、骨親和性が高い。また抗癌剤を複合したカーボンファイバーは、癌細胞を抑制するためのDDSとしての役割を果たすと、一転して骨形成の足場材となり、二重の働きを示した。このように、癌転移骨環境を制御する際に最終目標である骨欠損の修復にそれぞれの材料が寄与する治療法はまれであり、学術的意義が大きい。高齢化社会で癌骨転移の患者が増える中、本研究が臨床応用されれば患者のQOLと生存期間が延長し、社会的意義も大きいものとなる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (29 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (5 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Chonnam National University(韓国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Chonnam National University(韓国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Chonnnam National University(韓国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Chonnam National University(韓国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Chonnam National University(韓国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Ibandronate-Loaded Carbon Nanohorns Fabricated Using Calcium Phosphates as Mediators and Their Effects on Macrophages and Osteoclasts2021

    • Author(s)
      Maki Nakamura, Katsuya Ueda, Yumiko Yamamoto, Kaoru Aoki, Minfang Zhang, Naoto Saito, Masako Yudasaka
    • Journal Title

      ACS Applied Materials & Interfaces

      Volume: 13 Issue: 3 Pages: 3701-3712

    • DOI

      10.1021/acsami.0c20923

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolated lymphatic vessel lumen perfusion system for assessing nanomaterial movements and nanomaterial-induced responses in lymphatic vessels2021

    • Author(s)
      Kuroda Chika、Ajima Kumiko、Ueda Katsuya、Sobajima Atsushi、Yoshida Kazushige、Kamanaka Takayuki、Sasaki Jun、Ishida Haruka、Haniu Hisao、Okamoto Masanori、Aoki Kaoru、Kato Hiroyuki、Saito Naoto
    • Journal Title

      Nano Today

      Volume: 36 Pages: 101018-101018

    • DOI

      10.1016/j.nantod.2020.101018

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biokinetic Evaluation of Contrast Media Loaded Carbon Nanotubes Using a Radiographic Device2021

    • Author(s)
      Takasaka Mieko、Kobayashi Shinsuke、Usui Yuki、Haniu Hisao、Tsuruoka Shuji、Aoki Kaoru、Saito Naoto
    • Journal Title

      Toxics

      Volume: 9 Issue: 12 Pages: 331-331

    • DOI

      10.3390/toxics9120331

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor Effect of Sclerostin against Osteosarcoma2021

    • Author(s)
      Ideta Hirokazu、Yoshida Kazushige、Okamoto Masanori、Sasaki Jun、Kito Munehisa、Aoki Kaoru、Yoshimura Yasuo、Suzuki Shuichiro、Tanaka Atsushi、Takazawa Akira、Haniu Hisao、Uemura Takeshi、Takizawa Takashi、Sobajima Atsushi、Kamanaka Takayuki、Takahashi Jun、Kato Hiroyuki、Saito Naoto
    • Journal Title

      Cancers

      Volume: 13 Issue: 23 Pages: 6015-6015

    • DOI

      10.3390/cancers13236015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of MC3T3-E1 Cell Osteogenesis in Different Cell Culture Media.2021

    • Author(s)
      Izumiya M, Haniu M, Ueda K, Ishida H, Ma C, Ideta H, Sobajima A, Ueshiba K, Uemura T, Saito N, Haniu H.
    • Journal Title

      Int J Mol Sci.

      Volume: 22 Issue: 14 Pages: 7752-7752

    • DOI

      10.3390/ijms22147752

    • NAID

      120007124079

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbon fibers for treatment of cancer metastasis in bone2020

    • Author(s)
      Kamanaka Takayuki、Haniu Hisao、Tanaka Manabu、Takizawa Takashi、Aoki Kaoru、Okamoto Masanori、Sobajima Atsushi、Yoshida Kazushige、Ideta Hirokazu、Mimura Tetsuhiko、Ishida Haruka、Ueda Katsuya、Uemura Takeshi、Kim Jin Hee、Kim Yoong Ahm、Kato Hiroyuki、Saito Naoto
    • Journal Title

      RSC Advances

      Volume: 10 Issue: 55 Pages: 33071-33079

    • DOI

      10.1039/d0ra05992g

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials2020

    • Author(s)
      Sano Mahoko、Izumiya Makoto、Haniu Hisao、Ueda Katsuya、Konishi Kosuke、Ishida Haruka、Kuroda Chika、Uemura Takeshi、Aoki Kaoru、Matsuda Yoshikazu、Saito Naoto
    • Journal Title

      Nanomaterials

      Volume: 10 Issue: 7 Pages: 1374-1374

    • DOI

      10.3390/nano10071374

    • NAID

      120007113492

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbon nanotube-based biomaterials for orthopaedic applications2020

    • Author(s)
      Aoki Kaoru、Ogihara Nobuhide、Tanaka Manabu、Haniu Hisao、Saito Naoto
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 8 Issue: 40 Pages: 9227-9238

    • DOI

      10.1039/d0tb01440k

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiwall Carbon Nanotube Composites as Artificial Joint Materials2020

    • Author(s)
      Sobajima Atsushi、Okihara Takumi、Moriyama Shigeaki、Nishimura Naoyuki、Osawa Takako、Miyamae Kazutaka、Haniu Hisao、Aoki Kaoru、Tanaka Manabu、Usui Yuki、Sako Ken-ichi、Kato Hiroyuki、Saito Naoto
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 6 Issue: 12 Pages: 7032-7040

    • DOI

      10.1021/acsbiomaterials.0c00916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applications of Carbon Nanotubes in Bone Regenerative Medicine2020

    • Author(s)
      Tanaka Manabu、Aoki Kaoru、Haniu Hisao、Kamanaka Takayuki、Takizawa Takashi、Sobajima Atsushi、Yoshida Kazushige、Okamoto Masanori、Kato Hiroyuki、Saito Naoto
    • Journal Title

      Nanomaterials

      Volume: 10 Issue: 4 Pages: 659-659

    • DOI

      10.3390/nano10040659

    • NAID

      120007113491

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sclerostin expression in trabecular bone is downregulated by osteoclasts2020

    • Author(s)
      Masanori Koide, Teruhito Yamashita, Kohei Murakami, Shunsuke Uehara, Keigo Nakamura, Midori Nakamura, Mai Matsushita, Toshiaki Ara, Hisataka Yasuda, Josef M Penninger, Naoyuki Takahashi, Nobuyuki Udagawa, Yasuhiro Kobayashi
    • Journal Title

      Sci Rep .

      Volume: 10 Issue: 1 Pages: 13751-13751

    • DOI

      10.1038/s41598-020-70817-1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteoclast differentiation by RANKL and OPG signaling pathways2020

    • Author(s)
      Udagawa Nobuyuki、Koide Masanori、Nakamura Midori、Nakamichi Yuko、Yamashita Teruhito、Uehara Shunsuke、Kobayashi Yasuhiro、Furuya Yuriko、Yasuda Hisataka、Fukuda Chie、Tsuda Eisuke
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 39 Issue: 1 Pages: 19-26

    • DOI

      10.1007/s00774-020-01162-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different aggregation and shape characteristics of carbon materials affect biological responses in RAW264 cells.2018

    • Author(s)
      Kuroda C, Ueda K, Haniu H, Ishida H, Okano S, Takizawa T, Sobajima A, Kamanaka T, Yoshida K, Okamoto M, Tsukahara T, Matsuda Y, Aoki K, Kato H, Saito N.
    • Journal Title

      Int J Nanomed

      Volume: 13 Pages: 6079-6088

    • DOI

      10.2147/ijn.s172493

    • NAID

      120007100156

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨は生きている ‐骨粗鬆症の予防と治療‐2020

    • Author(s)
      宇田川 信之
    • Organizer
      第1回日本基礎老化学会市民フォーラム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Biological responses of human lymphatic endothelial cells to carbon nanomaterials.2019

    • Author(s)
      Sano M, Haniu H, Ueda K, Kuroda C, Aoki K, Saito N.
    • Organizer
      15th International Congress of Toxicology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 癌転移骨環境における抗癌剤複合carbon fiberの評価.2019

    • Author(s)
      鎌仲貴之, 出田宏和, 佐々木純, 傍島淳,吉田和薫,滝沢崇, 岡本正則, 青木薫, 羽二生久夫, 加藤博之, 齋藤直人.
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] カーボンナノホーンに対する骨関連細胞の細胞応答性評価.2019

    • Author(s)
      上田勝也, 傍島淳,吉田和薫,鎌仲貴之, 佐々木純, 羽二生久夫, 西村直之, 岡本正則, 青木薫, 齋藤直人.
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌転移骨環境における抗癌剤付加カーボンファイバーの評価.2018

    • Author(s)
      鎌仲貴之,佐々木純,傍島淳,吉田和薫,滝沢崇,岡本正則,青木薫,羽二生久夫,齋藤直人,加藤博之.
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DDSキャリア評価のための摘出リンパ管灌流システムの構築.2018

    • Author(s)
      黒田千佳, 安嶋久美子, 羽二生久夫, 石田悠, 上田勝也, 青木薫, 加藤博之, 齋藤直人.
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Carbon nanotube application and safety in artificial joint.2017

    • Author(s)
      Saito N.
    • Organizer
      EMN Meeting on Carbon Nanostructures
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Computer-assisted Surgery for Cervical Disorders in Rheumatoid Arthritis.2017

    • Author(s)
      Saito N.
    • Organizer
      The 7th Institute for Biomedical Sciences International Symposium: Symposium on Advanced Materials and 3D Printing for Biomedical Applications.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多層カーボンナノチューブ複合ポリエチレンから作製した擬似摩耗粉の細胞毒性2017

    • Author(s)
      傍島淳、羽二生久夫、綱嶋義貴、沖原巧、青木薫、岡本正則、安嶋久美子、田中学、滝沢崇、吉田和薫、鎌仲貴之、加藤博之、齋藤直人
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 低密度バイオマテリアルの新規安全性評価法の検討2017

    • Author(s)
      羽二生久夫、傍島淳、青木薫、石田悠、上田勝也、岡本正則、加藤博之、齋藤直人
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] ビスホスホネート含有カーボン粒子複合体及びその製造方法2020

    • Inventor(s)
      齋藤直人、青木薫、上田勝也、湯田坂雅子、中村真紀
    • Industrial Property Rights Holder
      国立大学法人信州大学、 国立研究開発法人産業技術総合研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-021816
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2023-01-30  

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