Nanotechnology. 2017 Sep 15;28(37):375101. doi: 10.1088/1361-6528/aa8393. Epub 2017 Aug 2.
The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 10-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-β-cyclodextrin (β-CD-(SH)) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between β-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.
目前的癌症治疗方法鼓励研究人员开发新型高效的纳米载体。由于其独特的纳米尺寸（直径 40-80nm，长度 200-500nm）和中空内腔，以及良好的生物相容性和低成本，海泡石纳米管（HNTs）是一种很好的纳米载体候选物。在我们的研究中，我们制备了一种叶酸介导的靶向和氧化还原触发的抗癌药物输送系统，使阿霉素（DOX）能够由于癌细胞表面过表达的叶酸受体而特异性地运输到肿瘤部位。此外，它可以被癌细胞中还原剂谷胱甘肽（GSH）释放，其中 GSH 的含量比细胞外基质高近 10 倍。一系列方法表明，巯基-β-环糊精（β-CD-（SH））成功地通过氧化还原响应的二硫键与 HNTs 结合，并且叶酸-聚乙二醇-金刚烷（FA-PEG-Ad）通过β-CD/Ad 之间的强络合作用固定在 HNTs 上。体外研究表明，在二硫苏糖醇（DTT）还原环境中 DOX 的释放速率急剧升高，在 10mM DTT 中 10h 内释放的 DOX 达到 70%，而在磷酸盐缓冲液（PBS）中即使在 79h 后也仅释放 40%的 DOX。此外，靶向 HNTs 可以被过表达叶酸受体的癌细胞特异性内吞，并与非靶向 HNTs 相比，显著加速癌细胞凋亡。体内研究进一步证实，靶向 HNTs 对荷瘤裸鼠具有最佳的治疗效果，且无明显副作用，而游离 DOX 对正常组织有损伤作用。综上所述，这种新型纳米载体系统显示出了靶向输送和控制抗癌药物释放的巨大潜力，为肿瘤治疗提供了一个潜在的平台。
