Since the discovery of d-amino acids, they have been considered inactive and have not been used as potent drugs. Here, we report that simple mixing with poly(vinyl alcohol) (PVA) unleashed latent potentials of d-amino acids in boron neutron capture therapy (BNCT). PVA formed boronate esters with seemingly useless boronated d-amino acids and induced tumor-associated amino acid transporter-superselective internalization and prolonged intracellular retention, accomplishing complete cure of tumors. The superselective internalization was achieved by switching the internalization pathway from ineffective pass through the transporter to the transporter-mediated endocytosis. The acidic environment in the endo−/lysosome dissociated the boronate esters and elicited the stealthiness of the drugs, preventing their externalization and prolonging intracellular retention time. In a subcutaneous tumor model, this system accomplished surprisingly high tumor-selective accumulation that could not be achieved by conventional approaches and induced drastic BNCT effects. PVA may be a unique material to unlock potentials of seemingly inert molecules.

中文翻译：

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聚（乙烯醇）增强一种基于惰性 d-氨基酸的药物用于硼中子俘获疗法


自从 d-氨基酸被发现以来，它们一直被认为是无活性的，没有被用作强效药物。在这里，我们报道了与聚乙烯醇 （PVA） 的简单混合在硼中子俘获疗法 （BNCT） 中释放了 d-氨基酸的潜在电位。PVA 与看似无用的硼化 d 氨基酸形成硼酸酯，诱导肿瘤相关氨基酸转运蛋白超选择性内化和延长细胞内滞留，完成肿瘤的完全治愈。通过将内化途径从无效的转运蛋白传递到转运蛋白介导的内吞作用来实现超选择性内吞。内切 - /溶酶体中的酸性环境解离硼酸酯并引发药物的隐蔽性，防止其外化并延长细胞内保留时间。在皮下肿瘤模型中，该系统实现了传统方法无法实现的令人惊讶的高肿瘤选择性积累，并诱导了剧烈的 BNCT 效应。PVA 可能是一种独特的材料，可以释放看似惰性分子的潜力。