Development of systemic therapy using nanoparticles incorporating glucose against gastrointestinal cancer.

• Project/Area Number: 25670578
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: INOUE Akira 大阪大学, 医学部附属病院, 医員 (90645053)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Hirofumi 大阪大学, 医学(系)研究科(研究院), 准教授 (30322184)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 超微細ナノ粒子 / スーパーアパタイト / 高濃度グルコースを内包した超微細ナノ粒子 / ドラッグデリバリーシステム / 難治性消化器癌 / 新規治療法 / 抗腫瘍効果 / ROS活性 / 新規ドラッグデリバリーシステム / スーパーアパタイト超微細ナノ粒子法 / 消化器癌に対する新規治療法 / 胞内ROS活性 / 新規癌治療法 / グルコース内包スーパーアパタイト超微細ナノ粒子

Outline of Final Research Achievements

Tumor targeting nanotechnology has recently made therapeutic progress. We previously reported a pH sensitive in vivo delivery system of doxorubicin, or microRNA, using carbonate apatite (CA) nanoparticles. In this research project, to further explore utility of CA in cancer therapy, we attempted to transport excess glucose into tumor cells by conjugating glucose (Glc) to the nanoparticle. The complex (CA-Glc) was 22.27nm in size and was pH sensitive and degradable at an acidic pH, resulting in the release of incorporated glucose. CA-Glc significantly reduced the growth of colon cancer cell lines. Intravenous injections successfully suppressed solid tumor growth. This effect could be at least in part due to up regulation of ROS activity. In mice and monkeys, intravenously injected CA-Glc complex resulted in no serious abnormalities in body weight or blood chemistry. These results suggested that this nanoparticle complex may be a novel anti-cancer reagent.

Research Products

• [Journal Article] A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour effects. (2015)
  • Author(s): Hirofumi Yamamoto, Xin Wu, Hiroyuki Nakanishi, Yuki Yamamoto, Mamoru Uemura, Taishi Hata, Junichi Nishimura, Ichiro Takemasa, Tsunekazu Mizushima, Jun-Ichi Sasaki, Satoshi Imazato, Nariaki Matsuura, Yuichiro Doki & Masaki Mori.
  • Journal Title: Scientific reports Volume: January Issue: 1 Pages: 1-7
  • DOI: 10.1038/srep07742
  • Peer Reviewed / Open Access
• [Patent(Industrial Property Rights)] グルコースと炭酸アパタイトを使用した抗癌剤 (2014)
  • Inventor(s): 山本浩文 他
  • Industrial Property Rights Holder: 山本浩文 他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-20