Zhang Huijuan, Ji Yandan, Chen Qianqian, Jiao Xiaojing, Hou Lin, Zhu Xiali, Zhang Zhenzhong
School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , China and.
J Drug Target. 2015;23(6):552-67. doi: 10.3109/1061186X.2015.1016437. Epub 2015 Mar 10.
Artemisinin (ART) is a kind of drug with an endoperoxide bridge which tends to react with Fe(2+) to generate radicals for killing cancer cells. However, simultaneous delivery of hydrophobic ART and Fe(2+) ions into cancer cells remains a major challenge. In this study, a multi-functional tumor-targeting drug delivery system employing hyaluronic acid-derivatized multi-walled carbon nanotubes (HA-MWCNTs) as drug carriers, transferrin (Tf) as targeting ligand and ART as a model drug for cancer treatment was constructed. This delivery system (HA-MWCNTs/Tf@ART) not only retained optical property of MWCNTs and cytotoxicity of ART but also demonstrated synergistic anti-tumor effect using ART and Tf. Compared with free ART, remarkably enhanced anti-tumor efficacy of this drug vehicle was realized both in cultured MCF-7 cells in vitro and in a tumor-bearing murine model in vivo, due to increased intracellular accumulation of ART and co-delivery of Tf and ART analogs. HA-MWCNTs/Tf@ART with laser irradiation demonstrated the highest inhibition effect compared to the other groups. This result may provide a new way of using promising natural drugs for cancer therapy.
青蒿素(ART)是一种带有内过氧化物桥的药物,它倾向于与Fe(2+)反应生成自由基以杀死癌细胞。然而,将疏水性的ART和Fe(2+)离子同时递送至癌细胞仍然是一个重大挑战。在本研究中,构建了一种多功能肿瘤靶向药物递送系统,该系统采用透明质酸衍生化的多壁碳纳米管(HA-MWCNTs)作为药物载体,转铁蛋白(Tf)作为靶向配体,ART作为癌症治疗的模型药物。该递送系统(HA-MWCNTs/Tf@ART)不仅保留了MWCNTs的光学性质和ART的细胞毒性,还利用ART和Tf展现出协同抗肿瘤作用。与游离ART相比,由于ART细胞内蓄积增加以及Tf和ART类似物的共同递送,该药物载体在体外培养的MCF-7细胞和体内荷瘤小鼠模型中均实现了显著增强的抗肿瘤功效。与其他组相比,经激光照射的HA-MWCNTs/Tf@ART表现出最高的抑制效果。这一结果可能为使用有前景的天然药物进行癌症治疗提供一种新方法。