In the current clinical boron neutron capture therapy (BNCT), p-boronophenylalanine (BPA) has been the most powerful drug owing to its ability to accumulate selectively within cancers through cancer-related amino acid transporters including LAT1. However, the therapeutic success of BPA has been sometimes compromised by its unfavorable efflux from cytosol due to their antiport mechanism. Here, we report that poly(vinyl alcohol) (PVA) can form complexes with BPA through reversible boronate esters in aqueous solution, and the complex termed PVA-BPA can be internalized into cancer cells through LAT1-mediated endocytosis, thereby enhancing cellular uptake and slowing the untoward efflux. In in vivo study, compared with clinically used fructose-BPA complexes, PVA-BPA exhibited efficient tumor accumulation and prolonged tumor retention with quick clearance from bloodstream and normal organs. Ultimately, PVA-BPA showed critically enhanced antitumor activity in BNCT. The facile technique proposed in this study offers an approach for drug delivery focusing on drug metabolism.

中文翻译：

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聚乙烯醇通过调节新陈代谢提高中子俘获疗法中对硼烷苯丙氨酸的治疗潜力。

在当前的临床硼中子俘获疗法（BNCT）中，对硼烷苯丙氨酸（BPA）由于其能够通过与癌症相关的氨基酸转运蛋白（包括LAT1）在癌症中选择性地蓄积，而成为最强大的药物。但是，由于BPA的反转运机制，其从细胞质中的不利流出有时会损害BPA的治疗成功。在这里，我们报道聚乙烯醇（PVA）可以通过水溶液中的可逆硼酸酯与BPA形成复合物，称为PVA-BPA的复合物可以通过LAT1介导的内吞作用被内化到癌细胞中，从而增强细胞摄取和放慢不良流出。在体内研究中，与临床使用的果糖-BPA复合物相比，PVA-BPA表现出有效的肿瘤蓄积和延长的肿瘤保留时间，并能从血液和正常器官中快速清除。最终，PVA-BPA在BNCT中显示出显着增强的抗肿瘤活性。本研究中提出的简便技术提供了一种专注于药物代谢的药物递送方法。