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Organic-Inorganic Hybrid Hollow Nanoparticles Suppress Oxidative Stress and Repair Damaged Tissues for Treatment of Hepatic Fibrosis

Research Project

Project/Area Number 17H03403
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Composite materials/Surface and interface engineering
Research InstitutionKyushu University

Principal Investigator

Hayashi Koichiro  九州大学, 歯学研究院, 准教授 (80580886)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
Keywordsナノ粒子 / ハイブリッド / ナノ医療 / 多機能性 / DDS / 刺激応答性 / ドラッグデリバリー / 有機-無機ハイブリッド / スマートマテリアル / ナノ材料
Outline of Final Research Achievements

We synthesized multifunctional organic-inorganic hybrid hollow nanoparticles (HNPs) containing silibinin. The HNPs were mainly composed of siloxanes and disulfides and had surface thiols. The disulfides were cleaved by intracellular glutathione and reduced to thiols, leading to the deformation of the HNPs. Silibinin molecules were released through the cracks formed by HNP deformation. Furthermore, the HNPs suppressed the generation of hydroxyl radicals, a major cause of liver fibrosis, via sulfenylation reactions of HNP thiols. Retinol-modified HNPs targeted Kupffer cells and hepatic stellate cells, which are essential for hepatic fibrogenesis. The combined suppression of hydroxyl radical generation and release of silibinin using the HNPs decreased the proportion of fibrotic tissues and improved hepatic function. The therapeutic efficacy was greater than can be achieved by the suppression of hydroxyl radical generation alone and the injection of silibinin alone.

Academic Significance and Societal Importance of the Research Achievements

肝硬変は、慢性肝炎やアルコールの過剰摂取、肥満による脂肪肝などにより肝臓が線維化し、本来の機能を果たせなくなった状態である。現在の肝硬変の治療は、食事療法、運動、肝移植であり、肝臓の線維化を引き起こす原因に対して治療を施す療法はなく、線維化した肝臓を正常状態に戻すことはできない(日本消化器学会)。厚労省の発表では、肝硬変の患者は全国で50万人にのぼり、5年生存率は僅か40%である。このような背景から、早期の治療法の開発が求められている。本研究では、ナノ粒子を静脈内注射により投与することで、マウスの肝組織修復、肝機能回復を達成できており、これは新規治療法となる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(38 results)

All 2020 2019 2018 2017 Other

All Journal Article (26 results) (of which Peer Reviewed: 26 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Granular Honeycombs Composed of Carbonate Apatite, Hydroxyapatite, and β-Tricalcium Phosphate as Bone Graft Substitutes: Effects of Composition on Bone Formation and Maturation2020

    • Author(s)
      Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa
    • Journal Title

      ACS Applied Bio Materials

      Volume: 3 Pages: 1787-1795

    • DOI

      10.1021/acsabm.0c00060

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physical and Histological Comparison of Hydroxyapatite, Carbonate Apatite, and -Tricalcium Phosphate Bone Substitutes2020

    • Author(s)
      Kunio Ishikawa, Youji Miyamoto, Akira Tsuchiya, Koichiro Hayashi, Kanji Tsuru, Go Ohe
    • Journal Title

      Materials Science and Engineering: C

      Volume: 11 Pages: 110848-110848

    • DOI

      10.3390/ma11101993

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bone regeneration using β-tricalcium phosphate (β-TCP) block with interconnected pores made by setting reaction of β-TCP granules2020

    • Author(s)
      Tansza Setiana Putri, Koichiro Hayashi, Kunio Ishikawa
    • Journal Title

      Journal of Biomedical Materials Research Part A

      Volume: 108 Pages: 625-632

    • DOI

      10.1002/jbm.a.36842

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of surface roughening and calcite coating of titanium on cell growth and differentiation2020

    • Author(s)
      Rui Shi, Koichiro Hayashi, LT Bang, Kunio Ishikawa
    • Journal Title

      Journal of Biomaterials Applications

      Volume: 34 Pages: 917-927

    • DOI

      10.1177/0885328219883765

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨髄様組織を形成するハニカムスキャフォード2020

    • Author(s)
      林幸壱朗
    • Journal Title

      BIO INDUSTRY

      Volume: 2 Pages: 24-33

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Honeycomb blocks composed of carbonate apatite, β-tricalcium phosphate, and hydroxyapatite for bone regeneration: effects of composition on biological responses2019

    • Author(s)
      Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa
    • Journal Title

      Materials Today Bio

      Volume: 4 Pages: 100031-100031

    • DOI

      10.1016/j.mtbio.2019.100031

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fabrication and Histological Evaluation of Porous Carbonate Apatite Block from Gypsum Block Containing Spherical Phenol Resin as a Porogen2019

    • Author(s)
      9.Yuta Sakemi, Koichiro Hayashi, Akira Tsuchiya, Yasuharu Nakashima, Kunio Ishikawa
    • Journal Title

      Materials

      Volume: 12 Pages: 3997-3997

    • DOI

      10.3390/ma12233997

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carbonate Apatite Micro-Honeycombed Blocks Generate Bone Marrow-Like Tissues as well as Bone2019

    • Author(s)
      Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa
    • Journal Title

      Advanced Biosystems

      Volume: 3 Pages: 1900140-1900140

    • DOI

      10.1002/adbi.201900140

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Li2CO3 addition on the microstructural and electrical properties of lead-free piezoelectric (Ba,Ca)(Ti,Zr)O3 ceramics sintered in air or a reducing atmosphere2019

    • Author(s)
      Shunki Kobayashi, Koichiro Hayashi, and Wataru Sakamoto
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 58 Issue: SL Pages: SLLC04-SLLC04

    • DOI

      10.7567/1347-4065/ab3a21

    • NAID

      210000156947

    • ISSN
      0021-4922, 1347-4065
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carbonate apatite granules with uniformly sized pores that arrange regularly and penetrate straight through granules in one direction for bone regeneration2019

    • Author(s)
      Koichiro Hayashi, Melvin L. Munar, Kunio Ishikawa
    • Journal Title

      Ceramics International

      Volume: 45 Pages: 15429-15434

    • DOI

      10.1016/j.ceramint.2019.05.042

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fabrication and Evaluation of Interconnected Porous Carbonate Apatite from Alpha Tricalcium Phosphate Spheres2019

    • Author(s)
      Kunio Ishikawa, Tya Arifta, Koichiro Hayashi, Kanji Tsuru
    • Journal Title

      JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS

      Volume: 印刷中 Pages: 269-277

    • DOI

      10.1002/jbm.b.34117

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of titania nanoparticle-dispersed hybrid membranes from allyloxytitanium and phosphonic acid derivatives for fuel cell2018

    • Author(s)
      Naoya Ozawa, Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo
    • Journal Title

      Journal of Membrane Science

      Volume: 563 Pages: 221-228

    • DOI

      10.1016/j.memsci.2018.05.072

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydroxyl Radical-Suppressing Mechanism and Efficiency of Melanin-Mimetic Nanoparticles2018

    • Author(s)
      Koichiro Hayashi, Atsuto Tokuda, Wataru Sakamoto
    • Journal Title

      INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

      Volume: 19 Pages: 2309-2309

    • DOI

      10.3390/ijms19082309

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Red Blood Cell-Shaped Microparticles with a Red Blood Cell Membrane Demonstrate Prolonged Circulation Time in Blood2018

    • Author(s)
      Koichiro Hayashi, Shota Yamada, Wataru Sakamoto, Eri Usugi, Masatoshi Watanabe, Toshinobu Yogo
    • Journal Title

      ACS BIOMATERIALS SCIENCE & ENGINEERING

      Volume: 4 Pages: 2729-2732

    • DOI

      10.1021/acsbiomaterials.8b00197

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellulose-based molecularly imprinted red-blood-cell-like microparticles for the selective capture of cortisol2018

    • Author(s)
      K. Hayashi, H. Hayashi, S. Yamada, W. Sakamoto, T. Yogo
    • Journal Title

      CARBOHYDRATE POLYMERS

      Volume: 193 Pages: 173-178

    • DOI

      10.1016/j.carbpol.2018.03.095

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Organic-Inorganic Hybrid Hollow Nanoparticles Suppress Oxidative Stress and Repair Damaged Tissues for Treatment of Hepatic Fibrosis2018

    • Author(s)
      Koichiro Hayashi, Takuma Maruhashi, Wataru Sakamoto, Toshinobu Yogo
    • Journal Title

      Advanced Functional Materials

      Volume: 28 Pages: 1706332-1706332

    • DOI

      10.1002/adfm.201706332

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis2018

    • Author(s)
      K. Hayashi, S. Yamada, W. Sakamoto, T. Yogo
    • Journal Title

      Biomaterials

      Volume: 156 Pages: 45-55

    • DOI

      10.1016/j.biomaterials.2017.11.031

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication of Lead-Free Piezoelectric Li2CO3-Added (Ba,Ca)(Ti,Sn)O3 Ceramics under Controlled Low Oxygen Partial Pressure and Their Properties2018

    • Author(s)
      Kouta Noritake, Wataru Sakamoto, Isamu Yuitoo, Teruaki Takeuchi, Koichiro Hayashi, Toshinobu Yogo
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 57 Issue: 2 Pages: 021501-021501

    • DOI

      10.7567/jjap.57.021501

    • NAID

      210000148589

    • ISSN
      0021-4922, 1347-4065
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effective impairment of myeloma cells and their progenitors by hyperthermia.2018

    • Author(s)
      Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, M. Hiasa, A. Bat-Erdene, Y. Maeda, M. Oura, M. Takahashi, M. Iwasa, T. Harada, S. Fujii, K. Kurahashi, S. Yoshida, K. Kagawa, I. Endo, K. Aihara, M. Ikuo, K. Itoh, Koichiro Hayashi, Michihiro Nakamura, Masahiro Abe
    • Journal Title

      Oncotarget.

      Volume: 9 Pages: 10307-10316

    • DOI

      10.18632/oncotarget.23121

    • NAID

      120006576960

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 磁場を使った医療技術2018

    • Author(s)
      林幸壱朗
    • Journal Title

      現代化学

      Volume: - Pages: 15-15

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relaxometric Property of Organosilica Nanoparticles Internally Functionalized with Iron Oxide and Fluorescent Dye for Multimodal Imaging2017

    • Author(s)
      Michihiro Nakamura, Koichiro Hayashi, Hitoshi Kubo, Takafumi Kanadani, Masafumi Harada, Toshinobu Yogo
    • Journal Title

      Journal of Colloid and Interface Science

      Volume: 492 Pages: 127-135

    • DOI

      10.1016/j.jcis.2017.01.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthesis of Inorganic-organic Hybrid Membranes Consisting of Organotrisiloxane Linkages and Their Fuel Cell Properties at Intermediate Temperatures2017

    • Author(s)
      Masaya Takemoto, Koichiro Hayashi, Shin-ichi Yamaura, Wei Zhang, Wataru Sakamoto, Toshinobu Yogo
    • Journal Title

      Polymer

      Volume: 120 Pages: 021501-021501

    • DOI

      10.1016/j.polymer.2017.05.065

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesoscopic Multimodal Imaging Provides New Insight to Tumor Tissue Evaluation: An Example of Macrophage Imaging of Hepatic Tumor using Organosilica Nanoparticles2017

    • Author(s)
      Michihiro Nakamura, Koichiro Hayashi, Hitoshi Kubo, Masafumi Harada, Keisuke Izumi, Yoshihiro Tsuruo, Toshinobu Yogo
    • Journal Title

      Sci Rep

      Volume: 7 Pages: 3953-3953

    • DOI

      10.1038/s41598-017-04043-7

    • NAID

      120006650111

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metallic Glass Separators for Fuel Cells at Intermediate Temperatures2017

    • Author(s)
      Masaya Takemoto, Masatomo Hattori, Koichiro Hayashi, Shin-ichi Yamaura, Wei Zhang, Wataru Sakamoto, Toshinobu Yogo
    • Journal Title

      Materials Letters

      Volume: 206 Pages: 87-90

    • DOI

      10.1016/j.matlet.2017.06.115

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Organic-Inorganic Hybrid Nanoparticles for Tracking the Same Cells Seamlessly at the Cellular, Tissue, and Whole Body Levels2017

    • Author(s)
      Koichiro Hayashi, Yusuke Sato, Hiroki Maruoka, Wataru Sakamoto, Toshinobu Yogo
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 印刷中 Pages: 1129-1135

    • DOI

      10.1021/acsbiomaterials.7b00181

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 診断・治療用有機-無機ハイブリッドナノ粒子の開発2017

    • Author(s)
      林幸壱朗
    • Journal Title

      セラミックデータブック2017/2018

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Multifunctional Organic-Inorganic Hybrid Hollow Nanoparticles for Treatment of Hepatic Fibrosis2019

    • Author(s)
      Koichiro Hayashi, Takuma Maruhashi, Wataru Sakamoto, Toshinobu Yogo
    • Organizer
      6th International Conference on Multifunctional, Hybrid and Nanomaterials
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多機能性微粒子の合成と医療応用2018

    • Author(s)
      林幸壱朗
    • Organizer
      第8回日本バイオマテリアル学会九州ブロック講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 有機-無機ハイブリッド中空ナノ粒子の合成と肝硬変治療への応用2018

    • Author(s)
      林 幸壱朗, 丸橋卓磨, 坂本 渉, 余語利信
    • Organizer
      2018年度セラミックス協会東海支部学術研究発表会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 有機-無機ハイブリッド中空ナノ粒子のone-pot合成と肝繊維症治療への応用2018

    • Author(s)
      林 幸壱朗, 丸橋卓磨, 坂本 渉, 余語利信
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] One-Pot Synthesis of Dual Stimulus-Responsive Degradable Organic-Inorganic Hybrid Hollow Nanoparticles for Fluorescence Image-Guided Trimodal Therapy2017

    • Author(s)
      Koichiro Hayashi
    • Organizer
      BIT’s 7th Annual World Congress of Nano Science & Technology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] One-Pot Synthesis of Organic-Inorganic Hybrid Hollow Nanoparticles for Fluorescence Image-Guided Trimodal Therapy2017

    • Author(s)
      Koichiro Hayashi
    • Organizer
      2nd International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多機能性ナノ・マイクロ粒子の作製と生物医学応用2017

    • Author(s)
      林幸壱朗
    • Organizer
      日本ゾル-ゲル学会第15回討論会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 多機能ナノ/マイクロ粒子の合成と診断・治療への応用2017

    • Author(s)
      林幸壱朗
    • Organizer
      第7回ナノカーボンバイオシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ハイブリッド中空ナノ粒子を用いた肝線維化治療2017

    • Author(s)
      林幸壱朗, 丸橋卓磨, 坂本渉, 余語利信
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://hyoka.ofc.kyushu-u.ac.jp/search/details/K006777/index.html

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 医用ハニカム構造体、成形型、および製造方法2020

    • Inventor(s)
      石川 邦夫、林 幸壱 朗、土谷 享、岸田 良、中島 康晴
    • Industrial Property Rights Holder
      石川 邦夫、林 幸壱 朗、土谷 享、岸田 良、中島 康晴
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-038167
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 炭酸アパタイト被覆材料およびその製造方法2020

    • Inventor(s)
      石川 邦夫、林 幸壱 朗、土谷 享、岸田 良、中島 康晴
    • Industrial Property Rights Holder
      石川 邦夫、林 幸壱 朗、土谷 享、岸田 良、中島 康晴
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-063503
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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