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Development of a novel radiosensitizer with inorganic nanoparticles

Research Project

Project/Area Number 18K07752
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionKobe University

Principal Investigator

Nishimura Hideki  神戸大学, 医学研究科, 客員准教授 (80444610)

Co-Investigator(Kenkyū-buntansha) 佐々木 良平  神戸大学, 医学部附属病院, 教授 (30346267)
赤坂 浩亮  神戸大学, 医学研究科, 医学研究員 (20707161)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywordsナノ粒子 / 過酸化チタン / 放射線増感 / 表面修飾技術 / 活性酸素種 / 活性酸素 / 放射線治療 / がん治療
Outline of Final Research Achievements

The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs). PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization.

Academic Significance and Societal Importance of the Research Achievements

今日の臨床のがん治療の現場において、有機的な化合物で放射線増感剤として認識され、広く臨床使用されているものはない。そのため、その現状を打破する画期的なアイデアとして無機ナノ粒子に着目し、開発を進めてきた。これまで世界的にも金ナノ粒子の効果が期待されてきたが、我々が開発した過酸化チタンナノ粒子は金ナノ粒子よりも過酸化水素の産生が協力であり、より強い放射線増感効果を示すことを世界で初めて実証した。今後は臨床応用を目指して、毒性の評価や有効性の非臨床試験などを一歩一歩進めていく。

Report

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

    (26 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 8 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Efficacy of Spacers in Radiation Therapy for Locally Advanced Pancreatic Cancer: A Planning Study2021

    • Author(s)
      KAWAGUCHI HIROKI、DEMIZU YUSUKE、MUKUMOTO NARITOSHI、ISHIHARA TAKEAKI、MIYAWAKI DAISUKE、KOMATSU SHOHEI、AKASAKA HIROAKI、SHINOTO MAKOTO、SHIOYAMA YOSHIYUKI、NAKAMURA KATSUMASA、FUKUMOTO TAKUMI、SASAKI RYOHEI
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 1 Pages: 503-508

    • DOI

      10.21873/anticanres.14801

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surgical spacer placement for proton radiotherapy in locally advanced pancreatic body and tail cancers: initial clinical results2021

    • Author(s)
      Dongha Lee et al.
    • Journal Title

      Radiation Oncology

      Volume: 16 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s13014-020-01731-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Titanium oxide nano-radiosensitizers for hydrogen peroxide delivery into cancer cells2021

    • Author(s)
      Morita Kenta、Nishimura Yuya、Nakamura Satoko、Arai Yuki、Numako Chiya、Sato Kazuyoshi、Nakayama Masao、Akasaka Hiroaki、Sasaki Ryohei、Ogino Chiaki、Kondo Akihiko
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 198 Pages: 111451-111451

    • DOI

      10.1016/j.colsurfb.2020.111451

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gold Nanoparticles Enhance EGFR Inhibition and Irradiation Effects in Head and Neck Squamous Carcinoma Cells2020

    • Author(s)
      Kashin Masahiko、Kakei Yasumasa、Teraoka Shun、Hasegawa Takumi、Yamaguchi Akinobu、Fukuoka Takao、Sasaki Ryohei、Akashi Masaya
    • Journal Title

      BioMed Research International

      Volume: 2020 Issue: 1 Pages: 1-10

    • DOI

      10.1155/2020/1281645

    • NAID

      120006940231

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Comparative Assessment of Mechanisms and Effectiveness of Radiosensitization by Titanium Peroxide and Gold Nanoparticles2020

    • Author(s)
      Hassan Mennaallah、Nakayama Masao、Salah Mohammed、Akasaka Hiroaki、Kubota Hikaru、Nakahana Makiko、Tagawa Tatsuichiro、Morita Kenta、Nakaoka Ai、Ishihara Takeaki、Miyawaki Daisuke、Yoshida Kenji、Nishimura Yuya、Ogino Chiaki、Sasaki Ryohei
    • Journal Title

      Nanomaterials

      Volume: 10 Issue: 6 Pages: 1125-1125

    • DOI

      10.3390/nano10061125

    • NAID

      120006878579

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours2019

    • Author(s)
      Nakayama Masao、Uehara Kazuyuki、Nishimura Hideki、Tamura Shuhei、Munetomo Yoshiki、Tsudou Shinji、Mayahara Hiroshi、Mukumoto Naritoshi、Geso Moshi、Sasaki Ryohei
    • Journal Title

      Reports of Practical Oncology & Radiotherapy

      Volume: 24 Issue: 4 Pages: 383-391

    • DOI

      10.1016/j.rpor.2019.06.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pattern of recurrence after CyberKnife stereotactic body radiotherapy for peripheral early non-small cell lung cancer2019

    • Author(s)
      Nakamura Masaki、Nishikawa Ryo、Mayahara Hiroshi、Uezono Haruka、Harada Aya、Hashimoto Naoki、Nishimura Hideki
    • Journal Title

      Journal of Thoracic Disease

      Volume: 11 Issue: 1 Pages: 214-221

    • DOI

      10.21037/jtd.2018.12.115

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] First-In-Human Phase 1 Study of a Nonwoven Fabric Bioabsorbable Spacer for Particle Therapy: Space-Making Particle Therapy (SMPT)2019

    • Author(s)
      Sasaki Ryohei、Demizu Yusuke、Yamashita Tomohiro、Komatsu Shohei、Akasaka Hiroaki、Miyawaki Daisuke、Yoshida Kenji、Wang Tianyuan、Okimoto Tomoaki、Fukumoto Takumi
    • Journal Title

      Advances in Radiation Oncology

      Volume: 4 Issue: 4 Pages: 729-737

    • DOI

      10.1016/j.adro.2019.05.002

    • NAID

      120006796509

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vivo tissue distribution and safety of polyacrylic acid-modified titanium peroxide nanoparticles as novel radiosensitizers2018

    • Author(s)
      Morita Kenta、Suzuki Takahiro、Nishimura Yuya、Matsumoto Kazuhisa、Numako Chiya、Sato Kazuyoshi、Nakayama Masao、Sasaki Ryohei、Ogino Chiaki、Kondo Akihiko
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: - Issue: 1 Pages: 30749-30751

    • DOI

      10.1016/j.jbiosc.2018.01.012

    • NAID

      40021601146

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gold nanoparticles enhance X?ray irradiation?induced apoptosis in head and neck squamous cell carcinoma in?vitro2018

    • Author(s)
      Teraoka Shun、Kakei Yasumasa、Akashi Masaya、Iwata Eiji、Hasegawa Takumi、Miyawaki Daisuke、Sasaki Ryohei、Komori Takahide
    • Journal Title

      Biomedical Reports

      Volume: 9(5) Pages: 415-420

    • DOI

      10.3892/br.2018.1142

    • NAID

      120006653292

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of dosimetric parameters in the treatment planning of magnetic resonance imaging-based intracavitary image-guided adaptive brachytherapy with and without optimization using the central shielding technique.2018

    • Author(s)
      Nishikawa R, Yoshida K, Ebina Y, Omoteda M, Miyawaki D, Ishihara T, Ejima Y, Akasaka H, Satoh H, Kyotani K, Takahashi S, Sasaki R.
    • Journal Title

      Journal of Radiation Research

      Volume: 印刷中 Issue: 3 Pages: 316-326

    • DOI

      10.1093/jrr/rry009

    • NAID

      120006477549

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Outcomes of Patients With Primary Sacral Chordoma Treated With Definitive Proton Beam Therapy2018

    • Author(s)
      Aibe Norihiro、Demizu Yusuke、Sulaiman Nor Shazrina、Matsuo Yoshirou、Mima Masayuki、Nagano Fumiko、Terashima Kazuki、Tokumaru Sunao、Hayakawa Tomokatsu、Suga Masaki、Daimon Takashi、Suzuki Gen、Hideya Yamazaki、Yamada Kei、Sasaki Ryohei、Fuwa Nobukazu、Okimoto Tomoaki
    • Journal Title

      International Journal of Radiation Oncology*Biology*Physics

      Volume: 100 Issue: 4 Pages: 972-979

    • DOI

      10.1016/j.ijrobp.2017.12.263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function2018

    • Author(s)
      Ishihara Takeaki、Yamada Kazunari、Harada Aya、Yukiue Haruhiro、Tanahashi Masayuki、Niwa Hiroshi、Matsui Takashi、Yokomura Koshi、Ejima Yasuo、Sasaki Ryohei
    • Journal Title

      Acta Oncologica

      Volume: 57 Issue: 9 Pages: 1232-1239

    • DOI

      10.1080/0284186x.2018.1468088

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ionizing radiation enhances paracellular permeability through alteration of intercellular junctions in cultured human lymphatic endothelial cells2018

    • Author(s)
      Megumi Kishimoto, Masaya Akashi, Yasumasa Kakei, Junya Kusumoto, Akiko Sakakibara, Takumi Hasegawa, Shungo Furudoi, Ryohei Sasaki, Takahide Komori
    • Journal Title

      Lymphatic Research and Biology

      Volume: 印刷中 Issue: 4 Pages: 390-396

    • DOI

      10.1089/lrb.2017.0072

    • NAID

      120006543332

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Efficacy of space-making radiotherapy (SMRT) using bioabsorbable spacer for locally advanced unresectable pancreatic cancer in a planning study2021

    • Author(s)
      Hiroki Kawaguchi
    • Organizer
      The 4 th International Cancer Research Symposium a Training for Oncology Professionals
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 過酸化チタンナノ粒子による免疫放射線治療増感効果の検討2020

    • Author(s)
      窪田 光、藤田 佳子、清水 康之、Mohammed Salah、岩下 和真、妹尾 悟史、川口 弘毅、小林 加奈、石原 武明、宮脇 大輔、吉田 賢史、西村 勇哉、荻野 千秋、佐々木 良平
    • Organizer
      第33回日本放射線腫瘍学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞から放出されたエクソソームによる放射線増感効果2020

    • Author(s)
      中岡 藍、仲波名 真希子、椋本 成俊、赤坂 浩亮、清水 康之、Mohammed Salah、石原 武明 、宮脇 大輔、佐々木 良平
    • Organizer
      第33回日本放射線腫瘍学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Titanium peroxide nanoparticle enhance the efficacy of immuno-radiotherapy via activated CD8+ T cell dependent antitumor effect in vivo2020

    • Author(s)
      Hikaru Kubota, Yoshiko Fujita, Mohammed Salah, Yasuyuki Shimizu, Hiroaki Akasaka, Ryohei Sasaki
    • Organizer
      American Society for Radiation Oncology 62nd Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エクソソームを介した腫瘍細胞への放射線増感効果2020

    • Author(s)
      中岡 藍、仲波名 真希子、椋本 成俊、赤坂 浩亮、清水 康之、Mohammed Salah、石原 武明 、宮脇 大輔、佐々木 良平
    • Organizer
      第63回日本放射線影響学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 限局性肝細胞癌に対するサイバーナイフ動体追尾定位放射線治療の長期成績2019

    • Author(s)
      馬屋原 博, 橋本 直樹, 原田 文,西村 英輝, 北谷 圭司, 岩下 和真, 薮内 伴憲, 川口 弘毅, 石原 武明, 妹尾 悟史, 溝延 数房, 上原 和之, 石田 淳,藤井 正彦, 佐々木 良平
    • Organizer
      第28回日本定位放射線治療学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 空気中に設定されたリファレンスポイントにおけるMU計算の正確性2019

    • Author(s)
      赤坂浩亮、椋本成俊、矢田隆一、王天縁、清水康之、中岡藍、高橋夕七、吉田賢史、宮脇大輔、石原武明、佐々木良平
    • Organizer
      日本放射線腫瘍学会
    • Related Report
      2019 Research-status Report
  • [Presentation] エクソソームを介した放射線応答に関する基礎的検討2019

    • Author(s)
      中岡藍、仲波名真希子、犬伏祥子、椋本成俊、赤坂浩亮、清水康之、森田健太、今崎剛、藤田佳子、西村勇哉、荻野千秋、仁田亮、佐々木良平
    • Organizer
      日本放射線腫瘍学会
    • Related Report
      2019 Research-status Report
  • [Presentation] In situステルス性獲得にもとづく長期血中滞留性金ナノ粒子内包分子インプリントナノゲルの創製2018

    • Author(s)
      北山 雄己哉, 山田 託也, 赤坂 浩亮, 西村 勇哉, 五十嵐 一紀, 松本 有, 佐々木 良平, 竹内 俊文
    • Organizer
      第40回日本バイオマテリアル学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 過酸化チタンナノ粒子の併用による放射線増感治療法の開発2018

    • Author(s)
      西村 勇哉, 森田 健太, 荻野 千秋, 犬伏 祥子, 佐々木 良平, 近藤 昭彦
    • Organizer
      第34回日本DDS学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 放射線治療のための金ナノ粒子内包分子インプリントポリマーナノゲルの開発2018

    • Author(s)
      北山 雄己哉, 山田 託也, 木口 健太朗, 吉田 碧衣, 赤坂 浩亮, 西村 勇哉, 五十嵐 一紀, 松本 有, 佐々木 良平, 竹内 俊文
    • Organizer
      第40回日本バイオマテリアル学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of exosome of radiation-induced cervical adenocarcinoma2018

    • Author(s)
      Sachiko Inubushi, Yoshiko Fujita, Rhohei Sasaki
    • Organizer
      "第10回日本RNAi研究会  第5回日本細胞外小胞学会"
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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