Alpha-mangostin (MGS) is a natural xanthone compound extracted from mangosteen pericarps. It has great potential as an excellent anticancer agent. However, the extremely low solubility of MGS in water seriously impedes its medical application. Previously, we found that cyclodextrin (CD)-based hyperbranched polymer nanoparticles (CDNPs) solubilize MGS by encapsulating it in the CD cavity and that their binding constants are 100 times higher than those of native CDs. Our findings suggested that CDNPs could be good carriers of MGS. Here, we prepared three types of CDNP from α-, β-, and ɣCDs and compared them in terms of MGS release and in vitro and in vivo anticancer efficacy. βCDNP/MGS demonstrated the greatest anticancer efficacy, while no efficacy was observed for the other CDNPs. MGS release from CDNPs/MGS can be explained by a model in which the slow and rapid modes are connected in series; before release, MGS must shift from the slow to the rapid mode. We assumed that the slow and rapid modes are related to the interior and surface CDs of CDNPs. βCDNP/MGS showed the slowest release in the slow mode. We assume that slow release in the slow mode is essential for MGS retention until the cancerous region is reached. We examined drug release behavior and anticancer efficacy of cyclodextrin-based nanoparticles (CDNPs) containing alpha-mangostin (MGS) in three different type of CDs (α-, β-, and γ-CD). βCDNP containing MGS demonstrated the best anticancer efficacy, while no efficacy was observed for the other CDNPs. Our findings suggested the anticancer efficacy might depend on the drug retention capability in which the interior and surface CDs in the CDNPs relate to the slow and rapid release modes, respectively. We assume the drug retention capability of slow release mode is important for performing the anticancer efficacy.

中文翻译：

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含有α-芒果苷的环糊精基超支化聚合物纳米粒子的抗癌功效

α-山竹素 (MGS) 是一种从山竹果皮中提取的天然呫吨酮化合物。它作为一种优良的抗癌剂具有巨大的潜力。然而，MGS在水中极低的溶解度严重阻碍了其医疗应用。以前，我们发现基于环糊精 (CD) 的超支化聚合物纳米粒子 (CDNP) 通过将 MGS 封装在 CD 腔中来溶解 MGS，并且它们的结合常数比天然 CD 的结合常数高 100 倍。我们的研究结果表明，CDNPs 可能是 MGS 的良好载体。在这里，我们从 α-、β- 和 ɣCDs 制备了三种类型的 CDNP，并在 MGS 释放和体外和体内抗癌功效方面对它们进行了比较。βCDNP/MGS 表现出最大的抗癌功效，而其他 CDNPs 没有观察到功效。CDNPs/MGS 的 MGS 释放可以用慢速模式和快速模式串联的模型来解释；在释放之前，MGS 必须从慢速模式切换到快速模式。我们假设慢速和快速模式与 CDNP 的内部和表面 CD 有关。βCDNP/MGS 在慢速模式下释放最慢。我们假设缓慢模式下的缓慢释放对于 MGS 保留至关重要，直到到达癌变区域。我们在三种不同类型的 CD（α-、β- 和 γ-CD）中检测了含有 α-芒果苷（MGS）的环糊精纳米粒子（CDNP）的药物释放行为和抗癌功效。含有 MGS 的 βCDNP 表现出最好的抗癌功效，而其他 CDNP 没有观察到功效。我们的研究结果表明，抗癌功效可能取决于药物保留能力，其中 CDNP 中的内部和表面 CD 分别与缓慢和快速释放模式相关。我们假设缓释模式的药物保留能力对于发挥抗癌功效很重要。