Synthesis and therapeutic effect of macromolecular antitumor drug, pH-sensitive human serum albumin conjugates of pirarubicin
| Project/Area Number |
19K16467
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Sojo University (2020)
Kyushu University of Health and Welfare (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | アルブミン / ドラッグデリバリーシステム / がん / ピラルビシン / 酸性環境応答性 |
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| Outline of Research at the Start |
ヒト血清アルブミン（Human Serum Albumin; HSA）は、生体適合性、血中滞留性、がん標的性に優れ、抗がん剤運搬体として非常に有用な生体高分子である。このHSAに抗がん剤ピラルビシン（THP）を結合させ、がん組織集積後にがん組織内（酸性環境）でTHPを遊離する環境応答性高分子化抗がん剤（HSA-THP）を開発する。動物実験でHSA-THPのがん組織集積性やTHP遊離性、そして抗がん作用や副作用を検討することで、HSA-THPが高い治療効果を発揮する副作用の少ない高分子化抗がん剤となるか検証する。
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| Outline of Final Research Achievements |
Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of pirarubicin (THP) (HSA-THP) via a hydrazine bond between HSA and THP. In this study, we synthesized two types of HSA-THP with different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH. And, both HSA-THPs showed a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the rapid liberation of free THP under acidic conditions. Moreover, both HSA-THPs exhibited antitumor effect without apparent adverse effects, and the antitumor effects were higher than free THP. These findings suggest that these types of HSA-THPs are promising candidates for further development.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ヒト血清アルブミン（HSA）とアントラサイクリン系抗がん剤ピラルビシン（THP）を用いた酸性環境応答性高分子化抗がん剤（HSA-THP）を開発した。酸性環境（がん組織環境）応答性や元のTHPより高い抗がん効果を示したことから、がん組織選択的に機能する、安全かつ効果的な高分子化抗がん剤治療が期待できる。また、シンプルな薬物送達システムであり、他の抗がん剤や抗がん剤の効果増強剤などへの応用も可能であり、高分子化抗がん剤治療の戦略が広がることが期待される。
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Report
(3 results)
Research Products
(5 results)
