Efficient drug delivery systems are required to increase drug concentrations at tumor sites and to reduce the side effects on normal cells. In this work, we developed a nanoscale drug delivery system based on graphene oxide (GO) and used it to load a disulfide prodrug of podophyllotoxin (DCM-S-PPT), which was linked by a thiol-specific cleavable disulfide bond. In order to improve the biocompatibility in physiological solution, GO was functionalized with 6-armed polyethylene glycol (PEG) and characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. By atomic force microscopy, the size distribution of the nanoparticles was shown to be 25~250 nm. DCM-S-PPT was loaded on GO-PEG via p–p stacking and hydrophobic interactions. The loading rate reached 138%. In vitro cytotoxicity assay showed that GO-PEG/DCM-S-PPT inhibited the proliferation of human cervical adenocarcinoma HeLa cells more than that of human normal kidney 293T cells, which was attributed to the different intracellular concentrations of GSH. After intravenous injection in mice bearing tumors, GO-PEG/DCM-S-PPT showed the better antitumor activity and less side effects than those of DCM-S-PPT and PPT. Compared with DCM-S-PPT or PPT, GO-PEG/DCM-S-PPT complex showed the best tumor-targeting and specific drug release. Our results provide a novel strategy for the combination of nanocarriers and modified chemotherapy drugs in the future.

需要有效的药物输送系统来增加肿瘤部位的药物浓度并减少对正常细胞的副作用。在这项工作中，我们开发了一种基于氧化石墨烯（GO）的纳米级药物递送系统，并用于装载鬼臼毒素（DCM-S-PPT）的二硫键前药，该药物通过硫醇特异性可裂解的二硫键连接。为了提高在生理溶液中的生物相容性，GO用6臂聚乙二醇（PEG）进行了功能化，并通过UV-Vis光谱，傅里叶变换红外光谱和热重分析进行了表征。通过原子力显微镜观察，纳米颗粒的尺寸分布显示为25〜250nm。DCM-S-PPT通过p-p堆积和疏水相互作用被装载在GO-PEG上。加载率达到138％。体外细胞毒性试验表明，GO-PEG / DCM-S-PPT对人宫颈癌HeLa细胞的抑制作用比对人正常肾293T细胞的抑制作用强，这归因于细胞内GSH浓度的不同。静脉注射荷瘤小鼠后，GO-PEG / DCM-S-PPT比DCM-S-PPT和PPT具有更好的抗肿瘤活性和更少的副作用。与DCM-S-PPT或PPT相比，GO-PEG / DCM-S-PPT复合物显示出最佳的肿瘤靶向性和特异性药物释放。我们的结果为将来纳米载体和改良化疗药物的结合提供了一种新策略。静脉注射荷瘤小鼠后，GO-PEG / DCM-S-PPT比DCM-S-PPT和PPT具有更好的抗肿瘤活性和更少的副作用。与DCM-S-PPT或PPT相比，GO-PEG / DCM-S-PPT复合物显示出最佳的肿瘤靶向性和特异性药物释放。我们的结果为将来纳米载体和改良化疗药物的结合提供了一种新策略。静脉注射荷瘤小鼠后，GO-PEG / DCM-S-PPT比DCM-S-PPT和PPT具有更好的抗肿瘤活性和更少的副作用。与DCM-S-PPT或PPT相比，GO-PEG / DCM-S-PPT复合物显示出最佳的肿瘤靶向性和特异性药物释放。我们的结果为将来纳米载体和改良化疗药物的组合提供了一种新策略。