Development of delivery system of platinum nanoparticles as reactive oxygen species scavengers for the treatment of metastatic prostate cancer

• Project/Area Number: 15K08600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Katsumi Hidemasa 京都薬科大学, 薬学部, 准教授 (30434666)
• Co-Investigator(Kenkyū-buntansha): 山本 昌 京都薬科大学, 薬学部, 教授 (00166779)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 薬学 / 薬剤学 / 薬物送達システム / ナノ粒子 / 白金 / 前立腺癌 / 化学修飾 / 活性酸素 / 体内動態制御 / 癌

Outline of Final Research Achievements

Reactive oxygen species (ROS) are involved in the metastatic prostate cancer. To prevent metastatic prostate cancer, we developed polyetheylene glycol (PEG) modified platinum-gold alloy nanoparticles, which exhibited ROS-scavenging activities and high plasma retention after intravenous injection. The high plasma retention of nanoparticles with PEG modification has some advantages for the targeted delivery of nanoparticles to the prostate tumor through enhanced permeability and retention (EPR) effect. However, the cellular uptake by prostate cancer cells could be limited by steric hindrance of PEG after the delivery of nanoparticles. Therefore, to enhance the cellular uptake and efficacy of nanoparticles in prostate cancer cells, we developed a prostate cancer-specific cleavable PEG system using PSA-sensitive cleavable peptide. These technologies are promising approaches for preventing metastatic prostate cancer.

Research Products

• [Presentation] Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on hepatic metastasis (2017)
  • Author(s): Hidemasa Katsumi, Shoko Maruyama, Kosuke Kusamori, Sakane Toshiyasu, Akira Yamamoto
  • Organizer: 6th FIP Pharmaceutical Sciences World Congress 2017
  • Int'l Joint Research
• [Presentation] Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on peritoneal dissemination of tumor cells. (2016)
  • Author(s): 勝見英正 他
  • Organizer: 43th Annual Meeting ＆ Exposition of the Controlled Release Society
  • Place of Presentation: Washington State Convention Center (Seattle, USA)
  • Year and Date: 2016-07-17
  • Int'l Joint Research
• [Presentation] Prevention of endotoxin-induced acute lung injury by intrapulmonary (2015)
  • Author(s): 勝見英正、山本 昌 他
  • Organizer: 42th Annual Meeting ＆ Exposition of the Controlled Release Society
  • Place of Presentation: Edinburgh International Conference Centre (UK)
  • Year and Date: 2015-07-26