Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan.
Int J Nanomedicine. 2013;8:2653-67. doi: 10.2147/IJN.S46054. Epub 2013 Jul 24.
The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.
本文展示了单壁碳纳米管(SWCNTs)的光热效应与抗癌药物阿霉素(DOX)相结合,用于靶向和加速乳腺癌细胞的破坏。开发了一种靶向药物递送系统,用于通过聚乙二醇生物功能化和与叶酸缀合的负载 DOX 的 SWCNTs 选择性杀死乳腺癌细胞。在我们的工作中,体外药物释放研究表明,药物(DOX)在生理 pH(pH 7.4)下结合,仅在较低 pH 下释放,即溶酶体 pH(pH 4.0),这是肿瘤环境的特征 pH。观察到 DOX 从 SWCNTs 持续释放长达 3 天。SWCNTs 在近红外(NIR)区域具有很强的光吸收。在这个特殊的光谱窗口中,生物系统高度透明。我们的研究报告称,在 800nm 激光照射下,SWCNTs 表现出很强的光热转换特性。SWCNTs 的这些光学特性为癌症治疗中的选择性光热消融开辟了道路。还观察到叶酸缀合的 NTs 通过受体介导的内吞作用机制内化和进入癌细胞。体外实验结果表明,激光有效破坏了癌细胞,而正常细胞则得以幸免。当将上述激光效应与 DOX 缀合的 SWCNTs 结合使用时,我们发现增强和加速了乳腺癌细胞的杀伤。因此,由激光、药物和 SWCNTs 组成的这种纳米药物递送系统有望成为一种有前途的选择性治疗方式,具有高效的治疗效果和低副作用。