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Active invasion of surface hetero-functionalized theranotics nanoparticles to tumor tissue

Research Project

Project/Area Number 16K01358
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionYamaguchi University

Principal Investigator

NAKAMURA Michihiro  山口大学, 大学院医学系研究科, 教授 (10314858)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsドラッグデリバリー / 有機シリカナノ粒子 / EPR効果 / 腫瘍 / ターゲティング / 診断と治療の一体化 / ナノ医療 / セラノスティクス / ターゲッティング / ナノバイオ / ナノ粒子 / インベージョン
Outline of Final Research Achievements

We performed integrated research and development of anchoring, route expansion, and active invasion for advanced delivery to tumor tissues. Nanoparticles with highly functionalized active invasion were investigated by integrating the optimized passive invasion with vasodilatory function, vascular disorder function, and extracellular matrix degrading function. The distribution density of nanoparticles in the tumor tissue, the degree of accumulation, and the histological changes of the tumor were comprehensively evaluated by multisided observation, and the optimal heterofunctionalization and administration method were examined. Furthermore, we were able to study and evaluate the therapeutic effects of theranostic nanoparticles that combine the therapeutic functions such as light irradiation, radiation irradiation, and magnetic field hyperthermia therapeutic effect with the imaging function.

Academic Significance and Societal Importance of the Research Achievements

本研究は腫瘍組織へのナノ粒子の送達のため、その障壁となる組織間質の線維化、低酸素化、酸性化などに対して、複数の機能を協奏的に発現できる粒子を作製する点で独創的であり、学術的意義が高い。また本研究で用いる有機シリカ粒子は申請者が独自に開発した粒子であり、海外では類似の構造を持つ多種の多機能化無機シリカ粒子が診断用イメー ジング剤として米国 FDA の認可のもと臨床治験が進められ、その有効性と安全性が報告されている。本研究の成果により腫瘍組織への集積が高く、 既存の医療用ナノ粒子より優れた日本発の医療用ナノ粒子として臨床応用の可能性が高まった。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(45 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (24 results) (of which Int'l Joint Research: 15 results,  Invited: 10 results) Book (1 results) Remarks (6 results) Funded Workshop (1 results)

  • [Int'l Joint Research] University of California, Los Angeles/City of Hope/University of South California(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of California Los Angels/City of Hope Cancer Center(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of California Los Angels/City of Hope Cancer Center(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Relationship between the glutathione-responsive degradability of thiol-organosilica nanoparticles and the chemical structures.2019

    • Author(s)
      Doura T, Nishio T, Tamanoi F. Nakamura M.
    • Journal Title

      Journal of Materials Research

      Volume: - Pages: 1266-1278

    • DOI

      10.1557/jmr.2018.501

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Biodegradability of disulfide-organosilica nanoparticles evaluated by soft X-ray photoelectron spectroscopy : cancer therapy implications.2019

    • Author(s)
      Mekaru H, Yoshigoe A, Nakamura M, Doura T, Tamanoi F.
    • Journal Title

      ACS Applied Nano Materials

      Volume: 2 Pages: 479-488

    • DOI

      10.1021/acsanm.8b02023

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Continuous infusion of PTH1-34 delayed fracture healing in mice2018

    • Author(s)
      Yukata Kiminori、Kanchiku Tsukasa、Egawa Hiroshi、Nakamura Michihiro、Nishida Norihiro、Hashimoto Takahiro、Ogasa Hiroyoshi、Taguchi Toshihiko、Yasui Natsuo
    • Journal Title

      Scientific Reports

      Volume: 8 Pages: 13175-13175

    • DOI

      10.1038/s41598-018-31345-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organosilica Nanoparticles and Medical Imaging2018

    • Author(s)
      Nakamura Michihiro
    • Journal Title

      The Enzymes

      Volume: 44 Pages: 137-173

    • DOI

      10.1016/bs.enz.2018.08.002

    • Related Report
      2018 Research-status Report
  • [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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Miniaturization of thiol-organosilica nanoparticles induced by an anionic surfactant.2018

    • Author(s)
      Doura T, Tamanoi F. Nakamura M.
    • Journal Title

      Journal of Colloid and Interface Science

      Volume: 526 Pages: 51-62

    • DOI

      10.1016/j.jcis.2018.04.090

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 有機シリカナノ粒子の作製と応用2017

    • Author(s)
      中村教泰
    • Journal Title

      顕微鏡

      Volume: 52 Pages: 170-173

    • NAID

      130007689197

    • Related Report
      2017 Research-status Report
  • [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
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-guided Trimodal Therapy2016

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

      Advanced Functional Materials

      Volume: 26 Pages: 8613-8622

    • DOI

      10.1002/adfm.201603394

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 物質機能変換のためのナノ構造体としての 有機シリカナノ粒子2020

    • Author(s)
      中村 教泰
    • Organizer
      第二回ミニシンポジウム 生命科学と物質科学の融合
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Organosilica Nanoparticles Toward Theranostic2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      7th China-Japan Symposium on Nanomedicine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Biomedical Imaging using Multifunctional Organosilica Nanoparticles2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      13th International Symposium on Nanomedicine (ISNM2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Macrophage Specificity: Identification of Polyethylene Glycol-Resistant Macrophages on Stealth Imaging in Vitro Using Fluorescent Organosilica Nanoparticles2019

    • Author(s)
      Michihiro Nakamura
    • Organizer
      ASCB/EMBO Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] セラノスティクスの実現に向けた多機能有機シリカナノ粒子の開発2019

    • Author(s)
      中村 教泰, 中村 純奈, 西尾 忠
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Macrophage Specificity: Identification of Polyethylene Glycol-Resistant Macrophages on Stealth Imaging in Vitro Using Fluorescent Organosilica Nanoparticles2019

    • Author(s)
      Nakamura, M.
    • Organizer
      Keystone Symposia Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Organosilica Nanoparticles for Single Cell Imaging, Analysis and Characterization.2018

    • Author(s)
      Nakamura, M.
    • Organizer
      6th Japan-China Symposium on Nanomedicine, Matsue, Shimane, Japan, 2018/5/27
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アニオン性界面活性剤を用いたチオール有機シリカナノ粒子の合成2018

    • Author(s)
      堂浦智裕、玉野井冬彦、中村教泰
    • Organizer
      日本ケミカルバイオロジー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 多機能有機シリカナノ粒子を用いたメソスコピック・マルチモーダルイメージング2018

    • Author(s)
      中村教泰
    • Organizer
      解剖地方会第73回中国・四国支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Innovative Projects of Yamaguchi University Graduate School of Medicine2018

    • Author(s)
      Yoshiyuki Asai, Takeshi Abe, Michihiro Nakamura, Tadashi Nishio and Makoto Furutani-Seiki
    • Organizer
      12th International Symposium on Nanomedicine(ISNM2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Potency of Polyethyleneimine-modified Organosilica Nanoparticle as Efficient Cell-labeling Reagent2018

    • Author(s)
      T. Nishio, T. Doura, Y. Isoe and M. Nakamura
    • Organizer
      12th International Symposium on Nanomedicine(ISNM2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Investigation on stealth effect of surface-functionalized organosilica nanoparticles with various molecular weight polyethylene glycol2018

    • Author(s)
      Y. Isoe, T. Nishio, and M. Nakamura
    • Organizer
      12th International Symposium on Nanomedicine(ISNM2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drug Delivery System using Organosilica Nanoparticles Conjugated with Doxorubicin2018

    • Author(s)
      N. Ariyoshi, T. Nishio, J. Nakamura, M. Nakamura
    • Organizer
      12th International Symposium on Nanomedicine(ISNM2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Syntheses, Characterization, and Biomedical Applications of Multifunctionalized Organosilica Nanoparticles.2018

    • Author(s)
      Michihiro Nakamura
    • Organizer
      10th Choshu London Symposium, Ube, Yamaguchi
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ナノ・イメージングと診断2018

    • Author(s)
      中村教泰
    • Organizer
      21世紀の医療とテクノロジーの展望シンポジウム、日本ライフサイエンスビル(東京・中央区)
    • Related Report
      2017 Research-status Report
  • [Presentation] Biomedical application of multifunctional organosilica nanoparticles.2017

    • Author(s)
      Michihiro Nakamura
    • Organizer
      Cancer Nanotechnology 2017 Summer Symposium, Los Angeles, USA
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ポリエチレンイミン修飾有機シリカ・ナノ粒子の開発と電子顕微鏡観察技術を用いた粒子評価2017

    • Author(s)
      安藤英紀、堂浦智裕、中村教泰
    • Organizer
      第26回DDSカンファランス、グランシップ、(静岡県静岡市)
    • Related Report
      2017 Research-status Report
  • [Presentation] チオール有機シリカナノ粒子の新規サイズ制御合成法の開発と蛍光性ナノ粒子合成への応用2017

    • Author(s)
      堂浦智裕、安藤英紀、中村教泰
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Multifunctional Organosilica Nanoparticles Toward Theranostic.2017

    • Author(s)
      Michihiro Nakamura
    • Organizer
      5th China-Japan Symposium on Nanomedicine , Suzhou, China
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mesoscopic Multimodal Imaging using Multifunctionalized Organosilica Nanoparticles.2017

    • Author(s)
      Michihiro Nakamura
    • Organizer
      11th International Symposium on Nanomedicine (ISNM2017), Sendai, Miyagi
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Photo-biomedical Application of Multifunctional Organosilica Nanoparticles2016

    • Author(s)
      Michihiro Nakamura
    • Organizer
      10th Anniversary International Symposium on Nanomedicine (ISNM2016) (Keynote Speech of Special Session )
    • Place of Presentation
      Auditorium of National Institute of Advanced Industrial Science and Technology (茨城県・つくば市)
    • Year and Date
      2016-11-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 多機能有機シリカナノ粒子の医学生物学的応用2016

    • Author(s)
      中村教泰
    • Organizer
      日本解剖学会第71回中国・四国支部学術集会
    • Place of Presentation
      岡山大学 鹿田キャンパス (岡山県・岡山市)
    • Year and Date
      2016-10-22
    • Related Report
      2016 Research-status Report
  • [Presentation] シリカナノ粒子の高機能セラノスティック2016

    • Author(s)
      中村教泰
    • Organizer
      第32回日本DDS学会学術集会(シンポジウム:次世代DDSのためのマテリアル戦略)
    • Place of Presentation
      グランシップ(静岡県コンベンションアーツセンター)(静岡県・静岡市)
    • Year and Date
      2016-06-29
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Multifunctionalized Organosilica Nanoparticles for Single Cell Imaging, Analysis and Characterization2016

    • Author(s)
      Michihiro Nakamura
    • Organizer
      The 4th Japan-China Symposium on Nanomedicine
    • Place of Presentation
      北九州国際会議場 (福岡県・北九州市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] シリカナノ粒子の高機能セラノスティクス (第27章) ドラッグデリバリーシステム-バイオ医薬品創成に向けた組織、細胞内、核内送達技術の開発2018

    • Author(s)
      中村教泰
    • Total Pages
      8
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313337
    • Related Report
      2018 Research-status Report
  • [Remarks] 山口大学大学院医学系研究科 器官解剖学講座

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~nanomed1/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 国立大学法人山口大学ナノ・セラノスティクス国際センター

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~nanomed1/iNTC-index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 山口大学大学院医学系研究科 器官解剖学講座(旧解剖学第一講座)

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~nanomed1/index.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 器官解剖学 (旧 解剖学第一)

    • URL

      http://www.med.yamaguchi-u.ac.jp/medicine/chair/basic_00.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 器官解剖学 (旧 解剖学第一) Organ Anatomy and Nanomedicine

    • URL

      http://www.med.yamaguchi-u.ac.jp/medicine/chair/basic_00.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 器官解剖学 (旧 解剖学第一) Organ Anatomy and Nanomedicine

    • URL

      http://ds.cc.yamaguchi-u.ac.jp/~org-anat/

    • Related Report
      2017 Research-status Report
  • [Funded Workshop] 12th International Symposium on Nanomedicine(ISNM2018)2018

    • Related Report
      2018 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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