School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China.
Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, Henan Province, China.
ACS Appl Mater Interfaces. 2016 Dec 14;8(49):33484-33498. doi: 10.1021/acsami.6b11839. Epub 2016 Nov 30.
Fe plays an essential role for artemisinin (ART)-based drugs in anticancer therapy. As a result, it is important to realize these two agents' cotransport for improving antitumor efficacy. We utilized a kind of alternating magnetic field (AMF) and tumor-responsive material-mesoporous FeO (mFeO)-to encapsulate ART. After that, the outer surface of mFeO was capped with multifunctional hyaluronic acid (HA), which was used not only as a smart gatekeeper but also as a tumor targeting moiety. In vitro and in vivo studies proved that ART can be encapsulated in HA-mFeO and protected by HA coating which could effectively avoid premature release during in vivo circulation. HA-mFeO/ART could be taken up by MCF-7 tumor cells via CD44 receptor-mediated endocytosis and locate at acidic lysosome. Subsequently, "HA gate" could be degraded by acidity and hyaluronidase. Then this system synchronously released Fe and ART at the same site. Fe can nonenzymatically convert ART to ROS for killing cancer cells. Under AMF irradiation, HA-mFeO could not only effectively convert electromagnetic wave into heat for tumor thermal therapy but also generate high levels of reactive oxygen species (ROS) for tumor dynamic therapy. These results demonstrated that the antitumor efficacy of HA-mFeO/ART in vivo significantly enhanced 3.7 times compared with free ART. Combining with AMF, it further improved 3.9 times (V/V0 of 0.11), suggesting the successful combined application of HA-mFeO/ART and AMF for tumor treatment. It is believed that HA-mFeO/ART is a promising system for Fe-dependent drugs to improve their therapeutic effect.
铁在基于青蒿素（ART）的药物的抗癌治疗中起着至关重要的作用。因此，实现这两种药物的共转运对于提高抗肿瘤疗效非常重要。我们利用一种交变磁场（AMF）和肿瘤响应性材料-介孔 FeO（mFeO）来包裹 ART。之后，mFeO 的外表面被多功能透明质酸（HA）覆盖，HA 不仅可用作智能门控，还可用作肿瘤靶向部分。体外和体内研究证明，ART 可以封装在 HA-mFeO 中，并通过 HA 涂层保护，这可以有效地避免体内循环过程中的过早释放。HA-mFeO/ART 可以通过 CD44 受体介导的内吞作用被 MCF-7 肿瘤细胞摄取，并定位在酸性溶酶体中。随后，“HA 门”可以被酸性和透明质酸酶降解。然后，该系统可以在同一部位同步释放铁和 ART。铁可以非酶促地将 ART 转化为 ROS 以杀死癌细胞。在 AMF 照射下，HA-mFeO 不仅可以有效地将电磁波转化为热能用于肿瘤热疗，还可以产生高水平的活性氧（ROS）用于肿瘤动态治疗。这些结果表明，与游离 ART 相比，HA-mFeO/ART 在体内的抗肿瘤疗效显著增强了 3.7 倍。与 AMF 结合后，进一步提高了 3.9 倍（V/V0 为 0.11），表明 HA-mFeO/ART 和 AMF 联合应用于肿瘤治疗取得了成功。可以相信，HA-mFeO/ART 是一种有前途的铁依赖性药物系统，可以提高其治疗效果。
