Reactive oxygen species-sensitive prodrug micelles

• Project/Area Number: 25750175
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Osaka University
• Principal Investigator: VAN DER VLIES Andre Jacobus 大阪大学, 工学(系)研究科(研究院), 研究員 (80648593)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ナノ粒子 / ボロン酸 / 活性酸素 / ドラッグデリバリー / Nanoparticle / anti cancer drug / drug delivery / Nanoparticles / Drug delivery / Polymer / ROS

Outline of Final Research Achievements

Cancer is one of the leading causes of death in the developed world. In order to deliver anti-cancer drugs to the tumor site polymeric nanoparticles (NPs) have been developed. The characteristic properties of the tumor such as the presence of reactive oxygen species (ROS) and decreased pH can be used as a stimulus to release the drug from the NPs. In this project the applicant aimed to prepare boronic acid-containing micelles that could release a drug in response to ROS. Due to problems with this approach a NP platform, also containining boronic acid groups was developed using a different approach. These NPs were able to scavenge H2O2. Furthermore these NPs could be modified using the Suzuki coupling reaction to incorporate drug moleules. The drug doxorubicin was conjugated via an acid sensitive hydrazone bond. These doxorubicin-NPs were cytotoxic in two different cancer cell lines and should enable drug release in the acidic tumor microenvironment.

Research Products

• [Presentation] Functionalization of Boronic Acid Nanoparticles for Drug Delivery Application (2015)
  • Author(s): Andre J. van der Vlies and Urara Hasegawa
  • Organizer: 第64回高分子学会年次大会
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2015-05-27 – 2015-05-29
• [Presentation] Functionalization of Boronic Acid Nanoparticles by Suzuki Coupling for Drug Delivery Application (2015)
  • Author(s): Andre J. van der Vlies and Urara Hasegawa
  • Organizer: 2015 MRS Spring Meeting & Exhibit
  • Place of Presentation: the Moscone West Convention Center (San Francisco, USA)
  • Year and Date: 2015-04-06 – 2015-04-10
• [Presentation] フェニルボロン酸含有ナノ粒子へのカテキン担持と抗酸化活性 (2014)
  • Author(s): 森崎 愛美, Andre J. van der Vlies,宇山浩, 長谷川麗
  • Organizer: 第61回高分子討論会
  • Place of Presentation: 長崎大学文教キャンパス（長崎県長崎市）
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] Suzuki Coupling-Functionalized Boronic Acid Nanoparticles for Drug Delivery (2014)
  • Author(s): Andre J. van der Vlies and Urara Hasegawa
  • Organizer: 26th European Conference on Biomaterials
  • Place of Presentation: the Liverpool Echo Arena and Convention Centre （Liverpool, UK)
  • Year and Date: 2014-08-31 – 2014-09-03