School of Pharmacy, Bengbu Medical College, Bengbu 233030, China.
Nanoscale. 2018 Oct 4;10(38):18387-18397. doi: 10.1039/c8nr03899f.
The treatment of metastatic tumors is highly desirable in clinics, which has also increased the interest in the design of nanoscale drug delivery systems. Bone metastasis is one of the most common pathways in the metastasis of breast cancer, and it is also an important cause for tumor recurrence and death. The aryl boronate group, as an acid-labile linker, has been introduced into nano-assemblies in recent years. Especially, as a proteasome inhibitor anticancer drug with a boric acid group, bortezomib can facilitate the formation of pH-sensitive aryl boric acid ester linkage with the catecholic group. In this study, bortezomib-loaded micelles with bone targeting properties were constructed for the treatment of breast cancer bone metastasis. The mixed micelles employed alendronate (ALN) as the bone-targeting ligand and encapsulated bortezomib-catechol conjugates as the cargo. In vitro and in vivo studies showed that compared with free drugs or control micelles, these prodrug micelles (ALN-NP) exhibited many favorable properties such as reduced systemic toxicity and improved therapeutic effects. Therefore, ALN-NP is promising as a nanovehicle for bone-targeting delivery of chemotherapeutic drugs. Furthermore, this study offers a novel strategy combining bone targeting and aryl boronate-based pH-responsive drug release for anti-metastasis therapy.
在临床上，转移性肿瘤的治疗是非常需要的，这也增加了人们对纳米级药物传递系统设计的兴趣。骨转移是乳腺癌转移最常见的途径之一，也是肿瘤复发和死亡的重要原因。芳基硼酸酯作为一种酸不稳定的连接物，近年来已被引入纳米组装体中。特别是硼酸基团的蛋白酶体抑制剂抗癌药物硼替佐米，可以与儿茶酚基团形成 pH 敏感的芳基硼酸酯键。在这项研究中，构建了具有骨靶向特性的硼替佐米载药胶束，用于治疗乳腺癌骨转移。该混合胶束采用阿仑膦酸钠（ALN）作为骨靶向配体，并包封了硼替佐米-儿茶酚缀合物作为药物。体外和体内研究表明，与游离药物或对照胶束相比，这些前药胶束（ALN-NP）具有许多有利的特性，如降低全身毒性和提高治疗效果。因此，ALN-NP 有望成为一种用于骨靶向递化疗药物的纳米载体。此外，这项研究为抗转移治疗提供了一种结合骨靶向和基于芳基硼酸的 pH 响应性药物释放的新策略。
