Development of tumor-targeting NO sustained release agent that enhances tumor accumulation of macromolecular antitumor drugs

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15327
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Sojo University
• Principal Investigator: Tsukigawa Kenji 崇城大学, 薬学部, 講師 (60772027)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 一酸化窒素 / アルブミン / 高分子化抗がん剤 / EPR効果 / 抗がん効果

Outline of Final Research Achievements

In this study, we developed a tumor-targeting nitric oxide (NO) sustained-releasing agent (HSA-NPB) by combining NO sustained-release agent (NPB) developed by our laboratory with human serum albumin (HSA), which has excellent tumor-targeting properties. HSA-NPB is designed to specifically and continuously act on tumor tissue with NO, and to enhance drug accumulation through a sustained increase in blood flow in tumor tissue. At first, we prepared HSA-NPB, in which two molecules of NPB are bound to one molecule of HSA, and confirmed the sustained release of NO. Then, we showed that the simultaneous administration of a macromolecular antitumor drug and HSA-NPB to tumor-bearing mice resulted in higher therapeutic efficacy than when the macromolecular antitumor drug was administered alone. These results indicate that HSA-NPB is a promising agent to enhance the tumor accumulation and therapeutic activity of macromolecular antitumor drug.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、NPBのNO徐放性とHSAのがん指向性を活用し、腫瘍組織の血流の持続的な増大と、それによる腫瘍集積性と治療効果の増強を企図した薬剤 HSA-NPBを開発した。高分子化抗がん剤の腫瘍集積性が低い場合、治療効果の減弱や副作用とともに、抗がん剤多量使用による医療費増大の要因となるため、腫瘍集積性の増強を志向した研究は極めて大きな意義がある。実際に高分子化抗がん剤と併用することで、単独時より高い治療効果が得られた。HSA-NPBは、種々の高分子化抗がん剤と併用できるため、がん治療戦略が広がることが期待される。