Zhang Huijuan, Hou Lin, Jiao Xiaojing, Yandan Ji, Zhu Xiali, Hongji Li, Chen Xiaozhe, Ren Junxiao, Xia Yadan, Zhang Zhenzhong
School of Pharmaceutical Sciences, Zhengzhou University, No.100, Kexue Road, Zhengzhou 450001, China.
Curr Pharm Biotechnol. 2014;14(13):1105-17. doi: 10.2174/1389201015666140408123710.
A multifunctional tumor-targeting drug delivery system employing single-walled carbon nanotubes (SWCNT) as drug carriers, AS1411 as targeting ligand and doxorubicine (DOX) as a model chemotherapy drug was constructed.
Firstly, SWCNT were modified with F68 (4.0 mg/ml) by ultrasonic dispersing technology due to the action of hydrophobic force and Van der Waals force, endowing SWCNT water dispersions and biocompatibility. Meanwhile, DOX could be easily absorbed on the surface of SWCNT by the π-π stacking, electrostatic adsorption and hydrophobic interactions. Finally, AS1411 was attached to the surface of DOX-SWCNT by the π-π stacking and electrostatic adsorption to obtain a tumor-targeting delivery system. Cellular uptake, anti-tumor effect in vitro and in vivo, cell cycle and apoptosis and biodistribution of AS1411-DOX-SWCNT were investigated, compared with the DOX solution.
This AS1411-mediated DOX-loaded SWCNT (AS1411-DOX-SWCNT) delivery system not only retained both optical properties of SWCNT and cytotoxicity of DOX but also could accumulate in tumors, which facilitated combination of chemotherapy and photothermal therapy. AS1411-DOX-SWCNT could effectively promote DOX cellular uptake and then increase intracellular accumulation as a targeting delivery system. AS1411-DOX-SWCNT by NIR laser excited could trigger S phase arrest and the late stage apoptotic on PC3 cancer cells. The investigation in vivo further confirmed that this system possessed higher tumor targeting capacity and antitumor efficacy than DOX, especially with NIR laser irradiation.
构建一种以单壁碳纳米管（SWCNT）为药物载体、AS1411为靶向配体、阿霉素（DOX）为模型化疗药物的多功能肿瘤靶向给药系统。
首先，利用超声分散技术在疏水力和范德华力作用下用F68（4.0mg/ml）修饰SWCNT，赋予SWCNT水分散性和生物相容性。同时，DOX可通过π-π堆积、静电吸附和疏水相互作用轻松吸附在SWCNT表面。最后，通过π-π堆积和静电吸附将AS1411连接到DOX-SWCNT表面，获得肿瘤靶向递送系统。研究了AS1411-DOX-SWCNT的细胞摄取、体内外抗肿瘤作用、细胞周期和凋亡以及生物分布，并与DOX溶液进行了比较。
这种AS1411介导的载DOX的SWCNT（AS1411-DOX-SWCNT）递送系统不仅保留了SWCNT的光学性质和DOX的细胞毒性，还能在肿瘤中蓄积，有利于化疗和光热疗法的联合应用。AS1411-DOX-SWCNT作为靶向递送系统可有效促进DOX的细胞摄取，进而增加细胞内蓄积。近红外激光激发的AS1411-DOX-SWCNT可诱导PC3癌细胞发生S期阻滞和晚期凋亡。体内研究进一步证实，该系统比DOX具有更高的肿瘤靶向能力和抗肿瘤疗效，尤其是在近红外激光照射下。
