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Development of specific molecular target therapy for oral cancer using new drug delivery system

Research Project

Project/Area Number 16K11698
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionTohoku University (2017-2018)
Kyushu Dental College (2016)

Principal Investigator

IWANAGA KENJIRO  東北大学, 歯学研究科, 助教 (20448484)

Co-Investigator(Kenkyū-buntansha) 西原 達次  九州歯科大学, 歯学部, 特任教授 (80192251)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords癌 / ソノポレーション / マイクロバブル / ナノバブル / ドラッグデリバリーシステム / 遺伝子導入
Outline of Final Research Achievements

Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions.In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated Microbubbles (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo. Bleomycin delivery using sonoporation with EGFR-MBs was significantly more toxic to the cells compared with the other groups.We next examined the effect of EGFR-MBs in a murine squamous cell carcinoma model. Bleomycin delivery by sonoporation with EGFR-MBs exhibited remarkable antitumor activity.
We focused novel platinum nanoparticles-conjugated latex beads, platinum nanocomposite(PtNCP) beads, and investigated the possibility to incorporate novel anti-cancer effect of these combined nanoparticles. PtNCP beads treatment suppressed tumor growth and identified increasing pathological necrotic areas, in vivo.

Academic Significance and Societal Importance of the Research Achievements

舌癌などは、表層から超音波を当てることができ,ソノポレーション法を用いる部位として適している.抗EGFR抗体修飾マイクロバブルは表面が水溶性ポリエチレングリコールで修飾されているため,肝臓などを中心とする細網内皮系組織の貪食細胞に処理されず,血中に長時間循環滞留することができる.バブルに抗EGFR抗体を結合させることにより,より選択的に癌局所へ抗癌物質を集積することができる.これらのバブルを用いれば,ターゲットとなる癌組織にバブルを集積させ,体外からの超音波診断とともに,治療用超音波エネルギーで,非侵襲的に抗癌剤を導入できる.口腔癌の治療を始め,様々な難治性疾患の治療に応用可能である.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Anticancer effect of novel platinum nanocomposite beads on oral squamous cell carcinoma cells2019

    • Author(s)
      Tanaka M., Okinaga T., Iwanaga K., Matsuo K., Toyono T., Sasaguri M., Ariyoshi W., Tominaga K., Enomoto Y., Matsumura Y., Nishihara, T.
    • Journal Title

      J Biomed Mater Res B Appl Biomater

      Volume: 9999B Issue: 7 Pages: 1-7

    • DOI

      10.1002/jbm.b.34320

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory response in LPS-driven human macrophages2018

    • Author(s)
      Kaneko Junya、Okinaga Toshinori、Ariyoshi Wataru、Hikiji Hisako、Fujii Seiko、Iwanaga Kenjiro、Tominaga Kazuhiro、Nishihara Tatsuji
    • Journal Title

      Cell Biology International

      Volume: 42 Issue: 12 Pages: 1622-1631

    • DOI

      10.1002/cbin.11058

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Epidermal growth factor receptor-targeted sonoporation with microbubbles enhances therapeutic efficacy in a squamous cell carcinoma model2017

    • Author(s)
      Hirabayashi F, Iwanaga K, Okinaga T, Takahashi O, Ariyoshi W, Suzuki R, Sugii M, Maruyama K, Tominaga K, Nishihara T
    • Journal Title

      PLoS One

      Volume: 12 Issue: 9 Pages: e0185293-e0185293

    • DOI

      10.1371/journal.pone.0185293

    • URL

      https://pure.teikyo.jp/en/publications/16425747-5a66-4027-a449-abe12cb94e0f

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of ultrasound and encapsulated doxorubicin bubble liposomes on cytotoxicity in human gingival squamous cell carcinoma Ca9-22 cells2017

    • Author(s)
      Ono, S., Iwanaga, K., Hirabayashi, F., Tominaga, K.
    • Journal Title

      J Kyushu Dent Soc.

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Application of combination bubble liposomal amphotericin B and sonication has the dramatic effect on oral candidiasis.2017

    • Author(s)
      Yamamoto, M., Iwanaga, K., Okinaga, T., Ariyoshi, W., Tominaga, K., Nishihara, T.
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology.

      Volume: 29 Issue: 3 Pages: 193-197

    • DOI

      10.1016/j.ajoms.2016.11.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Targeted drug delivery system using ultrasound and antibody-conjugated microbubbles enhances therapeutic efficacy in a squamous cell carcinoma model.2018

    • Author(s)
      Kenjiro Iwanaga, Fumika Hirabayashi, Kazuhiro Tominaga, Izumi Yoshioka, Takeyoshi Koseki, Tatsuji Nishihara
    • Organizer
      International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ten-year change of social capital status of oral health in local residents2018

    • Author(s)
      Syungo Watanabe, Kenjiro Iwanaga, Toru Tamahara, Mina Dodo, Wakana Iijima, Mana Igari, Tsubasa Kato, Atsushi Tanaka, Hitoshi Kiyonobu, Naoko Tanda, Takeyoshi Koseki
    • Organizer
      International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Kaikun is effective for preventing from trismus derived from treatment of head and neck cancer2018

    • Author(s)
      Toru Tamahara, Atsushi Tanaka, Kenjiro Iwanaga, Mina Dodo, Syungo Watanabe, Naoko Tanda, Wakana Iijima, Takeyoshi Koseki
    • Organizer
      International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oral management and infection control at the Perioperative Oral Support Center of Tohoku University Hospital2018

    • Author(s)
      Atsushi Tanaka, Toru Tamahara, Kenjiro Iwanaga, Mina Dodo, Tsubasa Kato, Syungo Watanabe, Naoko Tanda, Wakana Iijima, Mana Igari, Takeyoshi Koseki
    • Organizer
      International Symposium for Multimodal Research and Education in IOHS-Liaison 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 長期間の口腔管理を行った顎骨壊死症例について.2017

    • Author(s)
      渡辺俊吾 岩永賢二郎 玉原亨 百々美奈 飯嶋若菜 猪狩真奈 田中篤 清信仁 丹田奈緒子 小関健由
    • Organizer
      第7回東北口腔衛生学会総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 周術期口腔支援センターにおける診療の動向および取り組み2017

    • Author(s)
      岩永賢二郎 小関健由
    • Organizer
      第72回東北大学歯学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 術後性開口障害患者にかいくんを用いた開口訓練の効果について2017

    • Author(s)
      田中篤史 岩永賢二郎 玉原亨 百々美奈 飯嶋若菜 猪狩真奈 渡辺俊吾 加藤翼 清信仁 丹田奈緒子 小関健由
    • Organizer
      第21回日本歯科医療管理学会東北支部総会・学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Synergistic effects of antibody-conjugated microbubble and ultrasound on cytotoxicity of oral cell carcinoma cells2017

    • Author(s)
      Fumika Hirabayashi, Kenjiro Iwanaga, Toshinori Okinaga, Wataru Ariyoshi, Kazuhiro Tominaga, Izumi Yoshioka, Tatsuji Nishihara
    • Organizer
      The Tenth Japan-Korea Joint Symposium on Bio-microsensing Technology(10th JKBT)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 東北大学病院周術期口腔支援センターにおける診療の動向2017

    • Author(s)
      田中篤史 岩永賢二郎 玉原亨 百々美奈 飯嶋若菜 猪狩真奈 渡辺俊吾 加藤翼 丹田奈緒子 小関健由
    • Organizer
      第70回東北地区歯科医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 全身疾患をもつ高齢者の外来歯科治療における循環器系の全身的偶発症2017

    • Author(s)
      大渡凡人 曽我部浩一 岩永賢二郎 瀬田千尋 松田悠平 西原達次
    • Organizer
      第77回九州歯科学会総会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 九州歯科大学附属病院顎顔面外科における2015-2016新来患者の臨床統計学的観察2017

    • Author(s)
      朴真実 土生学 笹栗正明 上原雅隆 岩永賢二郎 吉賀大午 高橋理 三次翔 藤井誠子 早川真奈 冨永和宏
    • Organizer
      第77回九州歯科学会総会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔癌細胞増殖抑制における抗体付着マイクロバブルと超音波との相乗作用2016

    • Author(s)
      平林文香 岩永賢二郎 沖永敏則 有吉渉 西原達次
    • Organizer
      第58回歯科基礎医学会学術大会
    • Place of Presentation
      札幌市
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Tumor-specific drug delivery system using receptor-targeted microbubbles and ultrasound.2016

    • Author(s)
      平林文香 岩永賢二郎 沖永敏則 有吉渉 西原達次
    • Organizer
      Asia-Pacific Conference in Fukuoka 2016.
    • Place of Presentation
      北九州市
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔癌細胞株に対する抗体修飾マイクロバブルとソノポレーションを用いたdrug delivery systemの開発2016

    • Author(s)
      平林文香 岩永賢二郎 高橋理 冨永和宏
    • Organizer
      第70回NPO法人日本口腔科学会総会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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