2020 Fiscal Year Final Research Report
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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| 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 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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| Free Research Field |
医療薬学
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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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