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Design and Evaluation of Novel Nanomedicine for Periodontal Diseases

Research Project

Project/Area Number 24659920
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Periodontal dentistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

Yukio Nagasaki  筑波大学, 数理物質系, 教授 (90198309)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords歯周病 / ナノメディシン / 活性酸素 / レドックスインジェクタブルゲル / 酸化ストレス / 活性酵素 / 安定ラジカル / PICフラワーミセル / インジェクタブルゲル / 局所炎症モデル
Outline of Final Research Achievements

Reactive oxygen species (ROS) are considered to cause various disorders if they are produced in excess and become uncontrollable in the body. However, redox nanoparticle that effectively eliminates excess ROS has been developed and reported to be effective for the treatment of various systemic disorders. This particle is expected to be developed into drugs due to its high cost-performance, regional specificity, and few adverse effects. Therefore, to develop redox therapy for periodontitis, we designed novel Redox flower micelle, which disintegrates physiological conditions to form swollen gel (Redox Injectable Gel, RIG), allowing nitroxide radicals to act as a specific ROS scavenger, and evaluated inhibitory effects of RIG on Porphyromonas gingivalis (Pg)-induced bone loss in rat experimental periodontitis model. The results suggested the inhibitory effects of RIG on Pg-induced bone loss. It is promising as a therapeutic drug in the treatment on Pg-induced periodontitis.

Academic Significance and Societal Importance of the Research Achievements

歯周病は慢性的な歯肉炎が継続することにより、歯を保持している歯槽骨を非可逆的に破壊するのみならず、免疫系細胞が活性化し、過剰に発生した活性酸素は全身疾患にも強く関与していることが明らかになりつつあり、侮ることの出来ない疾患である。本研究では歯周ポケットに流し込むとゲル化し、持続的に活性酸素種を消去するレドックスインジェクタブルゲルを作製し、ラット歯周病モデルで評価したところ、高い効果で抗歯周病効果を発揮することを確認した。これは2017年時点で400万人を超え、益々増加する歯周病患者への治療法として高い社会的意義を有する。

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (44 results)

All 2013 2012 Other

All Journal Article (29 results) (of which Peer Reviewed: 27 results) Presentation (2 results) (of which Invited: 1 results) Book (12 results) Remarks (1 results)

  • [Journal Article] Redox-active injectable gel using thermo-responsive nanoscale polyion complex flower micelle for noninvasive treatment of local inflammation.2013

    • Author(s)
      Pua ML, Yoshitomi T, Chonpathompikunlert P, Hirayama A, Nagasaki Y
    • Journal Title

      J Control Release

      Volume: 172 Issue: 3 Pages: 914-920

    • DOI

      10.1016/j.jconrel.2013.10.009

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel protein PEGylation chemistry via glutalaldehydefunctionalized PEG, Bioconjugate Chemistry, Vol. 24, No.11, pp.1824-1827(2013) (doi: 10.1021/bc400169s)2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Bioconjugate Chemistry

      Volume: 11 Issue: 11 Pages: 1824-1827

    • DOI

      10.1021/bc400169s

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Coffee component Hydroxyl Hydro Quinone (HHQ) as a novel ligand for PPAR gamma and implications for breast cancer2013

    • Author(s)
      Babita Shashni, Karun Sharma, Rumani Singh, Kishore R Sakharkar, Sarinder K. Dhillon, Yukio Nagasaki, and Meena K. Sakharkar
    • Journal Title

      BMC (BioMedCentral) Genomics

      Volume: 14(Suppl 5):S6 Issue: S5

    • DOI

      10.1186/1471-2164-14-s5-s6

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Redox Nanoparticle Therapeutics to Cancer -Increase in therapeutic effect of doxorubicin, suppressing its adverse effect-2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Journal of Controlled Release

      Volume: 172 Issue: 1 Pages: 137-143

    • DOI

      10.1016/j.jconrel.2013.08.011

    • NAID

      120007130564

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design of sugar-oligonucleotide conjugates installed gold nanoparticle for effective delivery to hepatic parenchymal cells2013

    • Author(s)
      Yutaka Ikeda, Daisuke Kubota, Yukio Nagasaki
    • Journal Title

      Colloid and Polymer Science

      Volume: Vol. 291 Issue: 12 Pages: 2959-2964

    • DOI

      10.1007/s00396-013-3029-3

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of NSAID-induced Small Intestinal Inflammation by Orally Administered Redox Nanoparticles2013

    • Author(s)
      Sha Sha, Long Binh Vong, Pennapa Chonpathompikunlert, Toru Yoshitomi, Hirofumi Matsui, Yukio Nagasaki
    • Journal Title

      Biomaterials

      Volume: 34 Issue: 33 Pages: 8393-8400

    • DOI

      10.1016/j.biomaterials.2013.06.032

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-performance waveguide-mode biosensor for detection of Factor IX uses PEG-based blocking agents to suppress non-specific binding and improve sensitivity2013

    • Author(s)
      Thangavel Lakshmipriya, Makoto Fujimaki, Subash C.B. Gopinath, Koichi Awazu, Yukichi Horiguchi and Yukio Nagasaki
    • Journal Title

      Analyst

      Volume: Vol.138 Issue: 10 Pages: 2863-2870

    • DOI

      10.1039/c3an00298e

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-Performance Surface Acoustic Wave Immunosensing System on PEG/Aptamer Hybridized Surface,2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Langmuir

      Volume: 29 Issue: 24 Pages: 7369-7376

    • DOI

      10.1021/la304548m

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced intracellular drug delivery of pH-sensitive doxorubicin/poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) nanoparticles in multi-drug resistant human epidermoid KB carcinoma cells2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Biomaterials Science

      Volume: 1 Issue: 4 Pages: 361-367

    • DOI

      10.1039/c2bm00156j

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Facile solid-phase synthesis of a highly stable poly(ethylene glycol)-oligonucleotide conjugate2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 1 Issue: 4 Pages: 529-535

    • DOI

      10.1039/c2tb00031h

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The glycolytic enzymes PGK1 and PKM2 as novel transcriptional targets of PPAR gamma in breast cancer pathophysiology2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Journal of Drug Targeting

      Volume: 21 Issue: 2 Pages: 161-174

    • DOI

      10.3109/1061186x.2012.736998

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Biocompatible Nanoreactor for Silica/Gold Hybrid Nanoparticles Preparation2013

    • Author(s)
      長崎幸夫
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 102 Pages: 778-782

    • DOI

      10.1016/j.colsurfb.2012.09.034

    • NAID

      120007137069

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An Orally Administered Redox Nanoparticle that Accumlates in the Colonic Mucosa and Reduces Colitis in Mice2012

    • Author(s)
      Long Binh Vong, Tsutomu Tomita, Toru Yoshitomi, Hirofumi Matsui, Yukio Nagasaki
    • Journal Title

      Gastroenterology

      Volume: Vol.143, No.4 Issue: 4 Pages: 1027-1036

    • DOI

      10.1053/j.gastro.2012.06.043

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Different mechanisms of action of poly(ethylene glycol) and arginine on thermal inactivation of lysozyme and ribonuclease A2012

    • Author(s)
      Shunsuke Tomita
    • Journal Title

      Biotechnology and Bioengineering

      Volume: 109 Issue: 10 Pages: 2543-2552

    • DOI

      10.1002/bit.24531

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Redox Nanoparticle Treatment Protects Against Neurological Deficit in Focused Ultrasound-Induced Intracerebral Hemorrhage2012

    • Author(s)
      Pennapa Chonpathompikunlert, Ching-Hsiang Fan, Yuki Ozaki, Toru Yoshitomi, Chih-Kuang Yeh, Yukio Nagasaki
    • Journal Title

      Nanomedicine

      Volume: Vol.7, No.7 Issue: 7 Pages: 1029-1043

    • DOI

      10.2217/nnm.12.2

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a high-performance immunolatex based on "soft landing" antibody immobilization mechanism2012

    • Author(s)
      Xiaofei Yuan, Dolca Fabregat, Keitaro Yoshimoto and Yukio Nagasaki
    • Journal Title

      Colloid and Surface B: Biointreface

      Volume: Vol.99 Pages: 45-52

    • DOI

      10.1016/j.colsurfb.2011.09.040

    • NAID

      120007137228

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Boron Neutron Capture Therapy Assisted by Boron-conjugated Nanoparticles2012

    • Author(s)
      Shogo Sumitani, Yukio Nagasaki
    • Journal Title

      Polymer Journal

      Volume: Vol.44, No.6 Issue: 6 Pages: 522-530

    • DOI

      10.1038/pj.2012.30

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Design and preparation of a nanoprobe for imaging inflammation sites2012

    • Author(s)
      Toru Yoshitomi, Yukio Nagasaki
    • Journal Title

      Biointerphase

      Volume: 7 Issue: 1 Pages: 7-7

    • DOI

      10.1007/s13758-011-0007-5

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Block Ionomer Complexes of PEG-block-poly(4-vinylbenzylphosphonate) and Cationic Surfactants as Highly Stable, pH Responsive Drug Delivery System2012

    • Author(s)
      Masao Kamimura, Jong Oh Kim, Alexander V. Kabanov, Tatiana K. Bronich, and Yukio Nagasaki
    • Journal Title

      Journal of Controlled Release

      Volume: Vol.160 Issue: 3 Pages: 486-494

    • DOI

      10.1016/j.jconrel.2012.04.027

    • NAID

      120007137277

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term survival and functional maintenance of hepatocytes by using a microfabricated cell array2012

    • Author(s)
      Yutaka Ikeda, Tomoko Jomura, Umeko Horiuchi, Junko Saeki, Keitaro Yoshimoto, Takeshi Ikeya, Yukio Nagasaki
    • Journal Title

      Colloid and Surface, B, Biointerface

      Volume: 97 Pages: 97-100

    • DOI

      10.1016/j.colsurfb.2012.04.022

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improved Complementary Polymer Pair System: Switching for Enzyme Activity by PEGylated Polymers2012

    • Author(s)
      Takaaki Kurinomaru, Shunsuke Tomita, Shinpei Kudo, Sumon Ganguli, Yukio Nagasaki, Kentaro Shiraki
    • Journal Title

      Langmuir

      Volume: Vol.28, No.9 Issue: 9 Pages: 4334-4338

    • DOI

      10.1021/la2043312

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amemiya: Dependence of Swelling Behavior of pH-responsive PEG-modified Nanogel on Cross-link Density2012

    • Author(s)
      Goshu Tamura, Yuya Shinohara, Atushi Tamura, Yusuke Sanada, Motoi Oishi, Isamu Akiba, Yukio Nagasaki, Kazuo Sakurai, and Yoshiyuki
    • Journal Title

      Polymer Journal

      Volume: Vol.44,No.3 Issue: 3 Pages: 240-244

    • DOI

      10.1038/pj.2011.123

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PEGylation Technology in Nanomedicine2012

    • Author(s)
      Yutaka Ikeda, Yukio Nagasaki
    • Journal Title

      Advances in Polymer Science

      Volume: Volume 247, Polymers in Nanomedicine Pages: 115-140

    • DOI

      10.1007/12_2011_154

    • ISBN
      9783642278556, 9783642278563
    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics of core-polymerized, boron-conjugated micell es designed for boron neutron capture therapy for cancer2012

    • Author(s)
      Shogo Sumitani, Motoi Oishi, Tatsuya Yaguchi, Hiroki Murotani, Yukichi, Horiguchi, Minoru Suzuki, Koji Ono, Hironobu Yanagie, Yukio Nagasaki
    • Journal Title

      Biomaterials

      Volume: 33 Issue: 13 Pages: 3568-3577

    • DOI

      10.1016/j.biomaterials.2012.01.039

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Creation of a blood-compatible surface : a novel strategy for suppressing blood activation and coagulation using nitroxide radical-containing polymer with reactive oxygen species scavenging activity2012

    • Author(s)
      Toru Yoshitomi, Yu Yamaguchi, Akihiko Kikuchi, Yukio Nagasaki
    • Journal Title

      Acta Biomaterialia

      Volume: 8 Pages: 1323-1329

    • NAID

      120007130697

    • Related Report
      2013 Final Research Report
  • [Journal Article] 生体適合性ポリエチレングリコール表面の構築2012

    • Author(s)
      長崎幸夫
    • Journal Title

      高分子

      Volume: 61巻、2月号 Pages: 77-82

    • NAID

      10030169568

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] High PEGylation Efficiency of Pentaethylenehexamine-end Poly(ethyleneglycol) (mPEG-N6) for Active-ester Surface2012

    • Author(s)
      長崎幸夫
    • Journal Title

      Colloid and Surface B: Biointerface

      Volume: 92 Pages: 25-29

    • DOI

      10.1016/j.colsurfb.2011.11.013

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] High PEGylation Efficiency of Pentaethylenehexamine-end Poly(ethyleneglycol) (mPEG-N6) for Active-ester Surface2012

    • Author(s)
      Xiaofei Yuan, Dolca Fabregat, Keitaro Yoshimoto and Yukio Nagasaki
    • Journal Title

      Colloid and Surface B: Biointerface

      Volume: 92 Issue: 2 Pages: 25-29

    • DOI

      10.4155/tde.11.153

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Creation of a blood-compatible surface: a novel strategy for suppressing blood activation and coagulation using nitroxide radical-containing polymer with reactive oxygen species scavenging activity2012

    • Author(s)
      Toru Yoshitomi, Yu Yamaguchi, Akihiko Kikuchi, Yukio Nagasaki
    • Journal Title

      Acta Biomaterialia

      Volume: 8 Issue: 3 Pages: 1323-1329

    • DOI

      10.1016/j.actbio.2011.11.029

    • NAID

      120007130697

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Oral Redox Polymer Therapeutics2013

    • Author(s)
      Yukio Nagasaki
    • Organizer
      16th International Symposium on Recent Advances in Drug Delivery
    • Place of Presentation
      Salt Lake Cisty, Utah, U.S.A(他)
    • Related Report
      2013 Final Research Report
  • [Presentation] レドックスインジェクタブルゲルの設計と評価2012

    • Author(s)
      長崎 幸夫
    • Organizer
      第51回電子スピンサイエンス学会年会 (SEST2012)(招待講演)
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] Environmentally-Responsive Nanogels for siRNA Delivery", "Advanced Delivery and Therapeutic Applications of RNAi(Ed. by Kun Cheng, Ram, I. Mahato)2013

    • Author(s)
      Atsushi Tamura, Yukio Nagasaki
    • Total Pages
      534
    • Publisher
      Wiley
    • Related Report
      2013 Final Research Report
  • [Book] PEGylated Ceramic Nanophosphors for Near-infrared Fluorescence Bioimaging", eBook, "Hot topics in biomedical materials2013

    • Author(s)
      Masao Kamimura, Yukio Nagasaki
    • Publisher
      Future Science, London, U.K
    • Related Report
      2013 Final Research Report
  • [Book] 大腸粘膜に対する経口型レドックスナノ粒子の集積と潰瘍性大腸炎治療効果の増強」、「非経口投与製剤の開発と応用―次世代型医薬品の新規投与形態の開拓を目指して―」、山本昌監修2013

    • Author(s)
      長崎幸夫
    • Total Pages
      257
    • Publisher
      シーエム-シー出版
    • Related Report
      2013 Final Research Report
  • [Book] Environmentally-Responsive Nanogels for siRNA Delivery, Advanced Delivery and Therapeutic Applications of RNAi2013

    • Author(s)
      長崎幸夫
    • Total Pages
      150
    • Publisher
      Wiley
    • Related Report
      2013 Annual Research Report
  • [Book] PEGylated Ceramic Nanophosphors for Near-infrared Fluorescence Bioimaging2013

    • Author(s)
      長崎幸夫
    • Total Pages
      61
    • Publisher
      Future Science, London
    • Related Report
      2013 Annual Research Report
  • [Book] 大腸粘膜に対する経口型レドックスナノ粒子の集積と潰瘍性大腸炎治療効果の増強2013

    • Author(s)
      長崎幸夫
    • Total Pages
      257
    • Publisher
      シーエム-シー出版
    • Related Report
      2013 Annual Research Report
  • [Book] 「ガドリニウムフラーレンによる中性子捕捉療法」、2013ナノカーボン技術大全、Electric Journal編2012

    • Author(s)
      長崎幸夫、堀口諭吉
    • Total Pages
      250
    • Related Report
      2013 Final Research Report
  • [Book] 「ナノゲルによるピンポイント治療・診断システムへの展開」、先端バイオマテリアルハンドブック、秋吉一成(京都大学),石原一彦(東京大学),山岡哲二((独)国立循環器病研究センター研究所)監修2012

    • Author(s)
      長崎幸夫
    • Total Pages
      656
    • Publisher
      エヌ・ティー・エス、東京
    • Related Report
      2013 Final Research Report
  • [Book] PEGylatioPEGylation Technology in Nanomedicine, Advances in Polymer Science 247, Polymer s in Nanomedicinen Technology in Nanomedicine, Advances in Polymer Science 2472012

    • Author(s)
      Yutaka Ikeda, Yukio Nagasaki
    • Related Report
      2013 Final Research Report
  • [Book] ガドリニウムフラーレンによる中性子捕捉療法、2013ナノカーボン技術大全、20122012

    • Author(s)
      長崎幸夫
    • Total Pages
      5
    • Publisher
      Electric Journal
    • Related Report
      2012 Research-status Report
  • [Book] ナノゲルによるピンポイント治療・診断システムへの展開、先端バイオマテリアルハンドブック2012

    • Author(s)
      長崎幸夫
    • Total Pages
      6
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2012 Research-status Report
  • [Book] ナノ粒子アシスト型がん化学療法の開発2012

    • Author(s)
      長崎幸夫
    • Total Pages
      7
    • Publisher
      公益財団法人大阪癌研究会
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.ims.tsukuba.ac.jp/~nagasaki_lab/index.htm

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2024-01-30  

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