Targeted delivery of photosensitizers to uterine cervical cancer using iron oxide nanoparticles as a vehicle for effective photodynamic therapy

• Project/Area Number: 16K20187
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: amano tsukuru 滋賀医科大学, 医学部, 助教 (20613467)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 機能性ナノ粒子 / 光線力学療法 / 婦人科悪性腫瘍 / 子宮頸癌 / 卵巣癌 / 酸化鉄ナノ粒子 / ドラッグデリバリーシステム / phtodynamic therapy / drug celivery system

Outline of Final Research Achievements

In this work, a nanoparticle consisting of an Fe3O4 core, a polyglycerol brunching, and an octalysine functionality (SPION-PG-Lys8) has been synthesized and used to deliver a photosensitizer, chlorin e6 (Ce6), into cancer cells for photodynamic therapy (PDT) against cancer cells. In vitro experiment,SPION-PG-Lys8 is efficiently taken up by cancer cells, and showed low cytotoxicity. SPION-PG-Lys8/Ce6 is more easily taken up by the cells than free Ce6, and surprisingly, the internalized SPION-PG-Lys8/Ce6 is found to be enriched in the mitochondria. SPION-PG-Lys8/Ce6 exhibits almost no cytotoxicity under dark conditions, but strong photocytotoxicity due to the light-triggered production of reactive oxygen species (ROS) destroying the mitochondria. Our results highlight the great potential of SPION-PG-Lys8 as an efficient carrier of Ce6 for photodynamic cancer therapy.

Research Products

• [Journal Article] Preparationo of Rubst Metal-Free Magnetic Nanoemulsiions Encapsulating Low-Molecular-Weight Nitoxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery. (2017)
  • Author(s): Nagura, K., Takemoto, Y., Moronaga, S., Uchida, Y., Shimono, S., Shiino, A., Tanigaki, K., Amano, T., Yoshino, F., Noda, Y., Koizumi, S., Komatsu, N., Kato, T., Yamauchi, J., Tamura, R.
  • Journal Title: Chemisty A European Journal Volume: 23 Issue: 62 Pages: 15713-15720
  • DOI: 10.1002/chem.201702785
  • Peer Reviewed
• [Journal Article] Polyglycerol mediated covalent construction of magnetic mesoporous silica nanohybrid with aqueous dispersibility for drug delivery (2017)
  • Author(s): Yang Xiaoxin、Wen Yu、Wu Anqing、Xu Meiyun、Amano Tsukuru、Zheng Luyi、Zhao Li
  • Journal Title: Mater Sci Eng C Mater Biol Appl. Volume: 80 Pages: 517-525
  • DOI: 10.1016/j.msec.2017.06.022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Efficient Delivery of Chlorin e6 into Ovarian Cancer Cell with Octalysine Conjugated Superparamagnetic Iron Oxide Nanoparticle for Effective Photodynamic Therapy (2016)
  • Author(s): L. Zhao, H. Yang, T. Amano, H. Qin, L. Zheng, A. Takahashi, S. Zhao, I. Tooyama, T. Murakami, N. Komatsu
  • Journal Title: J. Mater. Chem. B Volume: 4 Issue: 47 Pages: 7741-7748
  • DOI: 10.1039/c6tb01988a
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant