Augmentation of tumor-target delivery of nanomedicine by an acid-responsive N-(2-hydroxypropyl)methacrylamide-based polymer-bradykinin conjugate.
| Project/Area Number |
18K06773
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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 47060:Clinical pharmacy-related
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| Research Institution | Sojo University |
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Principal Investigator |
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ブラジキニン / HPMAポリマー / 抗腫瘍効果 / ナノメディシン / ポリマー / 腫瘍 / EPR効果 / 抗がん効果 / 高分子性抗がん剤 |
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| Outline of Final Research Achievements |
In the present study, we designed and synthesized a novel N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugate of bradykinin (BK), which is an endogenous vasoactive peptide. Pretreatment with the polymer conjugate (P-BK) followed by administration of pegylated liposomal doxorubicin (PLD) in C26 tumor-bearing mice improved intratumoral blood flow (1.4-1.7 fold), increased tumor accumulation of PLD (approximately 3-fold), and demonstrated superior antitumor activity of PLD. Moreover, the combination significantly improved the survival rate of tumor-bearing mice. We believe that our study makes a significant contribution to the literature because the study findings suggest P-BK as a potential candidate to augment the enhanced permeability and retention (EPR) effect in tumors, and its concomitant use is expected to improve tumor delivery of nanomedicines.
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| Academic Significance and Societal Importance of the Research Achievements |
我国においては、およそ年間４０万人が「がん」を原因として亡くなっており、死因の第一位を占めている。また、抗体医薬品をはじめとする抗がん剤の高額化も医療財政上の大きな問題となってきている。本研究では、「がん病巣」への抗がん剤の集積性を増強する併用薬の創製に取り組むものである。本研究の結果より、本研究で創製したP-BKは、抗がん効果を維持したまま高分子性抗がん剤の投与量を減らす事が可能であることが示唆された。投与量の減少による副作用の減弱にもつながりうるものでもあり、高分子性抗がん剤を用いたがん治療をさらに発展しうる成果につながるものと期待している。
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Report
(4 results)
Research Products
(13 results)
