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Anticancer efficacy of cyclodextrin-based hyperbranched polymer nanoparticles containing alpha-mangostin


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.

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This work was supported by JSPS KAKENHI: Grant-in-Aid for Scientific Research (Grant No. 19K15394), Grant-in-Aid for Scientific Research A (20H00668), and Grant-in-Aid for Challenging Exploratory Research (20K20449).

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Correspondence to Shota Fujii or Kazuo Sakurai.

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Doan, V.T.H., Takano, S., Doan, N.A.T. et al. Anticancer efficacy of cyclodextrin-based hyperbranched polymer nanoparticles containing alpha-mangostin. Polym J 53, 481–492 (2021).

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