The feasibility of boron neutron capture therapy (BNCT) greatly depends on the selective accumulation of ¹⁰B in tumors. The p-boronophenylalanine-fructose (BPA-f) complex has been established as a conventional BNCT agent due to its preferential uptake into tumors, which is driven by amino acid transporters. However, the retention of BPA-f in tumors is highly limited because of an antiport mechanism, which is regulated by a gradient of amino acid concentration across the cancer cell membrane. Thus, to preserve a high ¹⁰B concentration in tumors, patients are inevitably subjected to a constant intravenous infusion. To this end, we employed a phenylboronic acid (PBA)-decorated polymeric nanoparticle (Nano^PBA) as a sialic acid-targeting BNCT agent. In this manner, the PBA can exhibit dual functionalities, i.e., exhibiting a neutron capture capacity and hypersialyated cancer cell targeting effect. Our developed Nano^PBA possesses a supramolecular structure composed of a core and shell comprised of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) segments, respectively. The PBA moiety is installed at the PEG end, providing an unusually strong targeting effect, supposedly via multivalent binding onto the cancer cell membrane. As in BNCT, we verified the feasibility of Nano^PBA against a B16 melanoma-bearing mouse model. By virtue of efficient tumor targeting, even at a 100-fold lower dose than BPA-f, the Nano^PBA achieved a potent antitumor effect.

硼中子俘获疗法（BNCT）的可行性在很大程度上取决于肿瘤中¹⁰ B的选择性积累。对-硼烷苯丙氨酸-果糖（BPA-f）复合物已被确立为常规BNCT药物，因为它优先吸收到肿瘤中，这是由氨基酸转运蛋白驱动的。然而，由于反端口机制，BPA-f在肿瘤中的保留受到高度限制，该机制由跨癌细胞膜的氨基酸浓度梯度来调节。因此，为了在肿瘤中保持高的¹⁰ B浓度，患者不可避免地要接受恒定的静脉内输注。为此，我们采用了苯硼酸（PBA）装饰的聚合物纳米颗粒（Nano ^PBA）作为靶向唾液酸的BNCT剂。以这种方式，PBA可以表现出双重功能，即表现出中子捕获能力和高唾液酸化的癌细胞靶向作用。我们开发的Nano ^PBA具有超分子结构，由核和壳组成，分别由聚乳酸（PLA）和聚乙二醇（PEG）段组成。PBA部分安装在PEG端，据推测是通过多价结合到癌细胞膜上而提供异常强的靶向作用。如在BNCT中一样，我们验证了纳米^PBA对抗B16黑色素瘤小鼠模型的可行性。凭借有效的肿瘤靶向能力，即使剂量比BPA-f低100倍，纳米^PBA 达到了有效的抗肿瘤作用。