Development of Innovative Anticancer Drug Delivery System for Malignant Glioma
| Project/Area Number |
18K08942
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Shiino Akihiko 滋賀医科大学, 神経難病研究センター, 准教授 (50215935)
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| Co-Investigator(Kenkyū-buntansha) |
田村 類 京都大学, 人間・環境学研究科, 名誉教授 (60207256)
谷垣 健二 滋賀県立総合病院(研究所), 神経病態研究部門, 専門研究員 (70362473)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性神経膠腫 / 分子標的 / 抗癌剤 / drug delivery system / がん幹細胞 / ファージディスプレイ / 血液脳関門 / 分子標的抗癌剤 / ファージディスプレイ法 / ナノエマルジョン / 悪性神経厚種 / 分子標的薬 / DDS / MRI |
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| Outline of Final Research Achievements |
We developped two molecularly targeted peptide probes using a phage display method. The probes pass through the blood brain barrier (BBB) and are specifically incorporated into malignant glioma (GBM) cells when administered intravenously. The peptides were attached to the surface of nanoemulsions (NEs), and the NEs were encapsulated with anticancer agents to create molecularly targeted anticancer agents for GBM. The antitumor effect was confirmed in the patient-derived xenograft (PDX) model, in which human-derived GBM stem cells are transplanted into the mouse brain.
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| Academic Significance and Societal Importance of the Research Achievements |
GBMの5年生存率は10%以下、平均余命は1～1.5年と予後不良である。この腫瘍は、浸潤性に進展するため切除範囲と脳の機能温存が対立し、手術で完全に摘出できない。血液脳関門(BBB)に守られ抗癌剤が届きにくい、という特徴があり、 ヒトのがんで最も治療が困難な疾患の1つである。研究者らは、頸静脈経由で腫瘍に特異的に輸送できるdrug delivery system(DDS)であるNEを開発した。本研究の特徴は、NE内に任意の抗癌剤を包埋できるので、多様な遺伝子変化をもつGBMに最も有効な抗癌剤カクテルを輸送できることにある。これまでに、このようなDDSの開発事例の報告はない。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Unique Suerparamagnetic-like Behavior Observed in Non-pi-delocalized Nitroxide Diradical Compounds Showing Discotic Liquid Crystalline Phase.2018
Author(s)
Takemoto, Y., Zaytseva, E., Suzuki, K., Yoshioka, N., Takanishi, Y., Funahashi, M., Uchida, Y., Akita, T., Park, J., Sato, S. Clevers, S., Coquerel, G., Mazhukin, D. G., Shimono, S., Sugiyama, M., Takahashi, H.,Yamauchi, J., Tamura, R.
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Journal Title
Chemistry A European Journal
Volume: 24
Issue: 65
Pages: 17293-17302
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Molecuoar Mobility Effect on Magnetic Interactions in All-Organic Paramagnetic Liquid Crystal with Nitroxide Radical as a Hydrogen-Bonding Acceptor.2018
Author(s)
Nakagami, S., Akita, T., Kiyohara, D., Uchida, Y., Tamura, R., Nishiyama, N.
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Journal Title
The Journal of Physical Chemistry B
Volume: 122
Issue: 29
Pages: 7409-7415
DOI
Related Report
Peer Reviewed
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[Presentation] Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery System.2018
Author(s)
K. Nagura, Y. Takemoto, S. Moronaga, Y. Uchida, S. Shimono, A. Shiino, K. Tanigaki, T. Amano, F. Yoshino, Y. Noda, S. Koizumi, N. Komatsu, T. Kato, J. Yamauchi, R. Tamura
Organizer
27th International Liquid Crystal Conference
Related Report
Int'l Joint Research
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[Presentation] Preparation and Characterization of MRI-Visible Nitroxide-Based Nanoemulsions Encapsulating Hydrophobic Fluorophores or Drugs.2018
Author(s)
K. Nagura, K. Sakamoto, S. Moronaga, A. Bogdanov, N. Chumakova, A. Kh. Vorobiev, H. Imai, T. Matsuda, A. Shiino, T. Amano, F. Yoshino, Y. Noda, S. Koizumi, S. Shimono, Y. Uchida, T. Kato, N. Komatsu, R. Tamura
Organizer
第八回ナノカーボンバイオシンポジウム
Related Report
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