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Development of novel bone-affinity nanoparticles and its application to cancer bone metastasis-specific drug discovery

Research Project

Project/Area Number 18K19656
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionMatsumoto Dental University

Principal Investigator

Hiraga Toru  松本歯科大学, 歯学部, 教授 (70322170)

Co-Investigator(Kenkyū-buntansha) 岩崎 泰彦  関西大学, 化学生命工学部, 教授 (90280990)
Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsがん / 骨転移 / 骨親和性ナノ粒子
Outline of Final Research Achievements

In the current study, we developed new nanoparticles that are expected to have high bone affinity and suppress uptake by reticuloendothelial cells, and investigated their effects on cancer bone metastasis. PMB-PEP nanoparticles were confirmed to have high bone affinity in vitro, but their ability to accumulate in bone tissue was not sufficient in vivo. Therefore, PMBA nanoparticles to which a bisphosphonate (alendronate) was added instead of PEP were prepared. High accumulation of PMBA nanoparticles in bone tissue was observed in vivo, and PMBA nanoparticles supplemented with an anticancer drug (docetaxel) significantly suppressed bone metastasis. These results suggest the possibility of applying PMBA nanoparticles to cancer bone metastasis-specific drug discovery.

Academic Significance and Societal Importance of the Research Achievements

本研究は未だ根治的な治療法が確立されていないがんの骨転移に対する革新的な治療法を提供すべく立案されたものである。本研究で開発されたナノ粒子は、①がん化学療法薬の骨転移特異的薬物送達、②ナノ粒子の送達効率を低下させることが問題視されている網内系細胞への捕捉の回避、を可能とした画期的な発明である。また、抗がん剤を付加することで、マウスモデルにおいて骨転移に対する有効性が示されたことから、今後の臨床応用が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (32 results)

All 2021 2020 2019 2018

All Journal Article (25 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 25 results,  Open Access: 8 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Particle-stabilized oil-in-water emulsions as a platform for topical lipophilic drug delivery.2021

    • Author(s)
      Hiranphinyophat S, Otaka A, Asaumi Y, Fujii S, Iwasaki Y
    • Journal Title

      Colloids Surf B Biointerfaces

      Volume: 197 Pages: 111423-111423

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitive and selective methanol biosensor using two-enzyme cascade reaction and fluorometry for non-invasive assessment of intestinal bacteria activity.2021

    • Author(s)
      Toma K, Iwasaki K, Arakawa T, Iwasaki Y, Mitsubayashi K
    • Journal Title

      Biosens Bioelectron

      Volume: 181 Pages: 113136-113136

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of Structural Coloration by Natural Sunlight Irradiation on a Melanin Precursor Polymer Inspired by Skin Tanning.2021

    • Author(s)
      Okoshi T, Iwasaki T, Takahashi S, Iwasaki Y, Kishikawa K, Kohri M
    • Journal Title

      Biomacromolecules

      Volume: - Issue: 4 Pages: 1730-1738

    • DOI

      10.1021/acs.biomac.1c00161

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone mineral affinity of polyphosphodiesters.2020

    • Author(s)
      Iwasaki Y
    • Journal Title

      Molecules

      Volume: 25 Issue: 3 Pages: 758-758

    • DOI

      10.3390/molecules25030758

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surfaces immobilized with oligo-prolines prevent protein adsorption and cell adhesion.2020

    • Author(s)
      Noguchi Y, Iwasaki Y, Ueda M, Kakinoki S
    • Journal Title

      J Mater Chem B

      Volume: 8 Issue: 11 Pages: 2233-2237

    • DOI

      10.1039/d0tb00051e

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone-targeting phospholipid polymers to solubilize the lipophilic anticancer drug.2020

    • Author(s)
      Otaka A, Yamaguchi T, Saisho R, Hiraga T, Iwasaki Y
    • Journal Title

      J Biomed Mater Res A

      Volume: 108 Issue: 10 Pages: 2090-2099

    • DOI

      10.1002/jbm.a.36968

    • NAID

      120007028170

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein patterning with antifouling polymer gel platforms generated using visible light irradiation.2020

    • Author(s)
      Iwasaki Y, Bunuasunthon S, Hoven VP
    • Journal Title

      Chem Commun (Camb)

      Volume: 56 Issue: 41 Pages: 5472-5475

    • DOI

      10.1039/d0cc02092c

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of novel surface coating composed of MDPB and MPC with dual functionality of antibacterial activity and protein repellency2020

    • Author(s)
      Thongthai Pasiree、Kitagawa Haruaki、Kitagawa Ranna、Hirose Nanako、Noree Susita、Iwasaki Yasuhiko、Imazato Satoshi
    • Journal Title

      Journal of Biomedical Materials Research Part B: Applied Biomaterials

      Volume: 108 Issue: 8 Pages: 3241-3249

    • DOI

      10.1002/jbm.b.34661

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skin ethanol gas measurement system with a biochemical gas sensor and gas concentrator toward monitoring of blood volatile compounds2020

    • Author(s)
      Arakawa Takahiro、Aota Takashi、Iitani Kenta、Toma Koji、Iwasaki Yasuhiko、Mitsubayashi Kohji
    • Journal Title

      Talanta

      Volume: 219 Pages: 121187-121187

    • DOI

      10.1016/j.talanta.2020.121187

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultra-Sensitive Isopropanol Biochemical Gas Sensor (Bio-Sniffer) for Monitoring of Human Volatiles.2020

    • Author(s)
      Chien PJ, Suzuki T, Ye M, Toma K, Arakawa T, Iwasaki Y, Mitsubayashi K
    • Journal Title

      Sensors (Basel)

      Volume: 20 Issue: 23 Pages: 6827-6827

    • DOI

      10.3390/s20236827

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone metastasis: interaction between cancer cells and bone microenvironment.2019

    • Author(s)
      Hiraga T
    • Journal Title

      J Oral Biosci

      Volume: 61 Issue: 2 Pages: 95-98

    • DOI

      10.1016/j.job.2019.02.002

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor-Marked Stromal Population from Adipogenic to Osteoblastic Lineage.2019

    • Author(s)
      Yang M, Arai A, Udagawa N, Zhao L, Nishida D, Murakami K, Hiraga T, Takao-Kawabata R, Matsuo K, Komori T, Kobayashi Y, Takahashi N, Isogai Y, Ishizuya T, Yamaguchi A, Mizoguchi T
    • Journal Title

      J Bone Miner Res

      Volume: 34 Issue: 10 Pages: 1952-1963

    • DOI

      10.1002/jbmr.3811

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity.2019

    • Author(s)
      Matsumura Y, Ito Y, Mezawa Y, Sulidan K, Daigo Y, Hiraga T, Mogushi K, Wali N, Suzuki H, Itoh T, Miyagi Y, Yokose T, Shimizu S, Takano A, Terao Y, Saeki H, Ozawa M, Abe M, Takeda S, Okumura K, Habu S, Hino O, Takeda K, Hamada M, Orimo A.
    • Journal Title

      Life Sci Alliance

      Volume: 2(4):e201900425. Issue: 4 Pages: 1-24

    • DOI

      10.26508/lsa.201900425

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immobilization of polyphosphoesters on poly(ether ether ketone) (PEEK) for facilitating mineral coating2019

    • Author(s)
      Shun Kunomura, Yasuhiko Iwasaki
    • Journal Title

      J. Biomater. Sci., Polym. Edn.

      Volume: in press Issue: 10 Pages: 861-876

    • DOI

      10.1080/09205063.2019.1595305

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Surface grafting polyphosphoesters on cellulose nanocrystals to improve the emulsification efficacy.2019

    • Author(s)
      Hiranphinyophat S, Asaumi Y, Fujii S, Iwasaki Y
    • Journal Title

      Langmuir

      Volume: 35 Issue: 35 Pages: 11443-11451

    • DOI

      10.1021/acs.langmuir.9b01584

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thermally assisted generation of protein-poly(ethylene sodium phosphate) conjugates with high mineral affinity2019

    • Author(s)
      Suita Norte, Yasuhiko Iwasaki
    • Journal Title

      ACS Omega

      Volume: 4 Issue: 2 Pages: 3398-3404

    • DOI

      10.1021/acsomega.8b03585

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Label-free specific detection and collection of c-reactive protein using zwitterionic phosphorylcholine-polymer-protected magnetic nanoparticles.2019

    • Author(s)
      Iwasaki S, Kawasaki H, Iwasaki Y
    • Journal Title

      Langmuir

      Volume: 35 Issue: 5 Pages: 1749-1755

    • DOI

      10.1021/acs.langmuir.8b01007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Real-time monitoring of skin ethanol gas by a high-sensitivity gas phase biosensor (bio-sniffer) for the non-invasive evaluation of volatile blood compounds.2019

    • Author(s)
      Arakawa T, Suzuki T, Tsujii M, Iitani K, Chien PJ, Ye M, Toma K, Iwasaki Y, Mitsubayashi K
    • Journal Title

      Biosens Bioelectron

      Volume: 129 Pages: 245-253

    • DOI

      10.1016/j.bios.2018.09.070

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zwitterionic interfaces: concepts and emerging applications special issue.2019

    • Author(s)
      Jiang S, Ishihara K, Iwasaki Y, Vancso J
    • Journal Title

      Langmuir

      Volume: 35 Issue: 5 Pages: 1055-1055

    • DOI

      10.1021/acs.langmuir.8b04183

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surface modification of macrophages with nucleic acid aptamers for enhancing the immune response against tumor cells.2019

    • Author(s)
      Sugimoto S, Iwasaki Y
    • Journal Title

      Bioconjug Chem

      Volume: 印刷中 Issue: 12 Pages: 4160-4167

    • DOI

      10.1021/acs.bioconjchem.8b00793

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice.2018

    • Author(s)
      Wakabayashi H, Wakisaka S, Hiraga T, Hata K, Nishimura R, Tominaga M, Yoneda T.
    • Journal Title

      J Bone Miner Metab

      Volume: 36(3) Issue: 3 Pages: 274-285

    • DOI

      10.1007/s00774-017-0842-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression and localization of CRAMP in rat tooth germ and during reparative dentin formation2018

    • Author(s)
      Horibe K, Hosoya A, Hiraga T, Nakamura H
    • Journal Title

      Clin Oral Invest

      Volume: - Issue: 7 Pages: 2559-2566

    • DOI

      10.1007/s00784-018-2353-x

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxic microenvironment and metastatic bone disease.2018

    • Author(s)
      Hiraga T
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 11 Pages: 3523-3523

    • DOI

      10.3390/ijms19113523

    • NAID

      120006771435

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of Alcohol Dehydrogenase for Exhaled Acetaldehyde2018

    • Author(s)
      Iitani Kenta、Chien Po-Jen、Suzuki Takuma、Toma Koji、Arakawa Takahiro、Iwasaki Yasuhiko、Mitsubayashi Kohji
    • Journal Title

      ACS Sensors

      Volume: 3 Issue: 2 Pages: 425-431

    • DOI

      10.1021/acssensors.7b00865

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment and characterization of a C57BL/6 mouse model of bone metastasis of breast cancer.2018

    • Author(s)
      Hiraga T, Ninomiya T
    • Journal Title

      J Bone Miner Metab

      Volume: - Issue: 2 Pages: 235-242

    • DOI

      10.1007/s00774-018-0927-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Bone targeting phospholipid polymers to solubilize lipophilic anticancer drugs.2020

    • Author(s)
      Otaka A, Yamaguchi T, Saisho R, Hiraga T, Iwasaki Y
    • Organizer
      11th World Biomaterials Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 修復象牙質形成過程における古典的Wnt シグナルの組織学的検討2019

    • Author(s)
      原 弥革力、堀部寛治、平賀 徹、中村浩彰
    • Organizer
      第88回松本歯科大学学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 古典的Wnt シグナルによるデンティンブリッジ形成機構の解析2019

    • Author(s)
      原 弥革力、堀部寛治、平賀 徹、中村浩彰
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] C57BL/6マウスを用いた新規乳がん骨転移モデルの開発2019

    • Author(s)
      平賀 徹、二宮 禎
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Analysis of PTH-induced osteoblastic differentiation from BM-MCSs.2018

    • Author(s)
      楊 孟雨、荒井 敦、宇田川信之、平賀 徹、小林泰浩、髙橋直之、溝口利英
    • Organizer
      第4回日本骨免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] デンティンブリッジ形成過程における古典的Wnt シグナルの役割2018

    • Author(s)
      原 弥革力、堀部寛治、平賀 徹、中村浩彰
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] C57BL/6マウスを用いた新規乳がん骨転移モデルの開発と病態解析2018

    • Author(s)
      平賀 徹
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2022-01-27  

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