Along with the successful commercialization of chemotherapeutics, such as doxorubicin and paclitaxel, numerous natural compounds have been investigated for clinical applications. Recently, curcumin (CUR), a natural compound with various therapeutic effects, has attracted attention for cancer immunotherapy. Most chemotherapeutics, however, have poor water solubility due to their hydrophobicity, which makes them less suited to biomedical applications; CUR is no exception because of its low bioavailability and extremely high hydrophobicity. In the present study, we developed an easy but effective strategy using the interaction between the 1,3-dicarbonyl groups of drugs and phenylboronic acid (PBA) to solubilize hydrophobic drugs. First, we verified the coordinate interaction between 1,3-dicarbonyl and PBA using 3,5-heptanedione as a model compound, followed by CUR as a model drug. A PBA-grafted hydrophilic polymer was used to form a nanoconstruct by coordination bonding with CUR, which then made direct administration of the nanoparticles possible. The nanoconstruct exhibited remarkable loading capability, uniform size, colloidal stability, and pH-responsive drug release, attributed to the formation of core–shell nanoconstructs by coordinate interaction. The therapeutic nanoconstructs successfully showed both chemotherapeutic and anti-PD-L1 anticancer effects in cellular and animal models. Furthermore, we demonstrated the applicability of this technique to other 1,3-dicarbonyl compounds. Overall, our findings suggest a facile, but expandable strategy by applying the coordinate interaction between 1,3-dicarbonyl and PBA, which enables high drug loading and stimuli-responsive drug release.

中文翻译：

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基于苯基硼酸的核壳药物递送平台通过配位相互作用固定 1,3-二羰基化合物

随着化疗药物（如阿霉素和紫杉醇）的成功商业化，许多天然化合物已被研究用于临床应用。近年来，具有多种治疗作用的天然化合物姜黄素（CUR）在癌症免疫治疗中备受关注。然而，大多数化学治疗剂由于其疏水性而具有较差的水溶性，这使得它们不太适合生物医学应用；CUR 也不例外，因为其低生物利用度和极高的疏水性。在本研究中，我们开发了一种简单但有效的策略，利用药物的 1,3-二羰基与苯基硼酸 (PBA) 之间的相互作用来溶解疏水性药物。首先，我们使用 3,5-庚二酮作为模型化合物验证了 1,3-二羰基和 PBA 之间的配位相互作用，其次是 CUR 作为模型药物。使用 PBA 接枝的亲水聚合物通过与 CUR 的配位键合形成纳米结构，然后直接施用纳米颗粒成为可能。由于通过配位相互作用形成核壳纳米结构，纳米结构表现出显着的负载能力、均匀的尺寸、胶体稳定性和pH响应性药物释放。治疗性纳米结构在细胞和动物模型中成功显示出化疗和抗 PD-L1 抗癌作用。此外，我们证明了该技术对其他 1,3-二羰基化合物的适用性。总的来说，我们的研究结果通过应用 1,3-二羰基和 PBA 之间的协调相互作用提出了一种简便但可扩展的策略，这使得高载药量和刺激响应性药物释放成为可能。