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An Intelligent and Tumor-Responsive Fe2+ Donor and Fe2+-Dependent Drugs Cotransport System
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2016-11-30 00:00:00 , DOI: 10.1021/acsami.6b11839 Huijuan Zhang 1, 2, 3 , Qianqian Chen 1 , Xiaoge Zhang 1 , Xing Zhu 1 , Jianjiao Chen 1 , Hongling Zhang 1 , Lin Hou 1, 2, 3 , Zhenzhong Zhang 1, 2, 3
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2016-11-30 00:00:00 , DOI: 10.1021/acsami.6b11839 Huijuan Zhang 1, 2, 3 , Qianqian Chen 1 , Xiaoge Zhang 1 , Xing Zhu 1 , Jianjiao Chen 1 , Hongling Zhang 1 , Lin Hou 1, 2, 3 , Zhenzhong Zhang 1, 2, 3
Affiliation
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Fe2+ 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 Fe3O4 (mFe3O4)—to encapsulate ART. After that, the outer surface of mFe3O4 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-mFe3O4 and protected by HA coating which could effectively avoid premature release during in vivo circulation. HA-mFe3O4/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 Fe2+ and ART at the same site. Fe2+ can nonenzymatically convert ART to ROS for killing cancer cells. Under AMF irradiation, HA-mFe3O4 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-mFe3O4/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-mFe3O4/ART and AMF for tumor treatment. It is believed that HA-mFe3O4/ART is a promising system for Fe2+-dependent drugs to improve their therapeutic effect.
中文翻译：
一种智能的肿瘤反应性Fe 2+供体和Fe 2+依赖药物共转运系统
Fe 2+对于基于青蒿素（ART）的药物在抗癌治疗中起着至关重要的作用。因此，重要的是要实现这两种药物的共同转运以提高抗肿瘤功效。我们利用一种交变磁场（AMF）和肿瘤反应性材料-介孔Fe 3 O 4（mFe 3 O 4）来封装ART。之后，在mFe 3 O 4的外表面上盖上多功能透明质酸（HA），该透明质酸不仅用作智能门卫，还用作肿瘤靶向部分。体外和体内研究证明，ART可以封装在HA-mFe 3 O 4中并由HA涂层保护，可有效避免体内循环过程中的过早释放。HAFmFe 3 O 4 / ART可以通过CD44受体介导的内吞作用被MCF-7肿瘤细胞吸收，并位于酸性溶酶体上。随后，“ HA gate”可能会被酸度和透明质酸酶降解。然后，该系统在同一位置同步释放Fe 2+和ART。Fe 2+可以通过非酶将ART转化为ROS，从而杀死癌细胞。在AMF照射下，HA-mFe 3 O 4不仅可以有效地将电磁波转化为热量用于肿瘤热疗，还可以产生高水平的活性氧（ROS）用于肿瘤动态疗法。这些结果表明，与游离ART相比，HA-mFe 3 O 4 / ART在体内的抗肿瘤功效显着提高了3.7倍。与AMF联合使用，可进一步提高3.9倍（V / V0为0.11），表明HA-mFe 3 O 4 / ART和AMF成功地联合应用治疗了肿瘤。相信HA-mFe 3 O 4 / ART是用于Fe 2+依赖性药物以改善其治疗效果的有前途的系统。
更新日期：2016-11-30
中文翻译：
一种智能的肿瘤反应性Fe 2+供体和Fe 2+依赖药物共转运系统
Fe 2+对于基于青蒿素（ART）的药物在抗癌治疗中起着至关重要的作用。因此，重要的是要实现这两种药物的共同转运以提高抗肿瘤功效。我们利用一种交变磁场（AMF）和肿瘤反应性材料-介孔Fe 3 O 4（mFe 3 O 4）来封装ART。之后，在mFe 3 O 4的外表面上盖上多功能透明质酸（HA），该透明质酸不仅用作智能门卫，还用作肿瘤靶向部分。体外和体内研究证明，ART可以封装在HA-mFe 3 O 4中并由HA涂层保护，可有效避免体内循环过程中的过早释放。HAFmFe 3 O 4 / ART可以通过CD44受体介导的内吞作用被MCF-7肿瘤细胞吸收，并位于酸性溶酶体上。随后，“ HA gate”可能会被酸度和透明质酸酶降解。然后，该系统在同一位置同步释放Fe 2+和ART。Fe 2+可以通过非酶将ART转化为ROS，从而杀死癌细胞。在AMF照射下，HA-mFe 3 O 4不仅可以有效地将电磁波转化为热量用于肿瘤热疗，还可以产生高水平的活性氧（ROS）用于肿瘤动态疗法。这些结果表明，与游离ART相比，HA-mFe 3 O 4 / ART在体内的抗肿瘤功效显着提高了3.7倍。与AMF联合使用，可进一步提高3.9倍（V / V0为0.11），表明HA-mFe 3 O 4 / ART和AMF成功地联合应用治疗了肿瘤。相信HA-mFe 3 O 4 / ART是用于Fe 2+依赖性药物以改善其治疗效果的有前途的系统。
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