Augmentation of EPR effect and therapeutic effect of nanomedicine by improving tumor microenvironment
| Project/Area Number |
16K08217
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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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| Research Field |
Physical pharmacy
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| Research Institution | Sojo University |
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Principal Investigator |
FANG Jun 崇城大学, 薬学部, 准教授 (20412736)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | EPR効果 / DDS / 腫瘍ターゲティング / ナノメディシン / 一酸化窒素 / 一酸化炭素 / 腫瘍微小環境 / ニトログリセリン / アルギニン / ヒドロキシウレア / ドラッグデリバリー / 腫瘍 |
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| Outline of Final Research Achievements |
In this study, we have investigated approaches to augment EPR effect/tumor drug delivery of macromolecular nanomedicines, by improving tumor blood flow. For this aim, we focused on vascular mediators involved in EPR effect, i.e., nitric oxide (NO) and carbon monoxide (CO), and examined their potentials to enhance the delivery of nanomedicines into tumor, by using NO/CO generators. The NO/CO generators induced the generation of NO/CO more selectively in tumor, which in turn resulted in the improvement of tumor blood flow and increase of nano-drugs in tumor (EPR effect). Consequently, by combining with these NO/CO generators, the anticancer effect of nanomedicines were significantly elevated which were verified in different solid tumor models including carcinogen-induced cancers. These findings strongly suggested the potentials of these NO/CO generators as EPR enhancers to improve the therapeutic effects of nanomedicines.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、腫瘍血流の改善による副作用の少ないEPR効果/高分子抗がん治療の増強法を確立できると考えられる。その結果、高分子抗がん剤の腫瘍内デリバリーが数倍から数十倍増加でき、より効率の良い、これまで以上優れた抗がん治療効果が得られる。つまり、本研究の成果はがんの効率的な治療へとつながり、医療費の削減ならびにがん患者のQOLを上げることに寄与するものと強く期待される。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines.2018
Author(s)
Islam, W., Fang, J., Imamura, T., Etrych, T., Subr, V., Ulbrich K., & Maeda, H.
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Journal Title
Mol. Cancer Therap.
Volume: 17
Issue: 12
Pages: 2643-2653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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