Graphene oxide (GO) nanosheet is a drug delivery system due to its structural properties, which can be augmented in presence of folic acid (FA). This study aimed to compare the efficacy of GO as a passive (GO/DOX) and active (GO/FA/DOX) forms for delivering doxorubicin (DOX). These two forms of conjugates were characterized before and after loading of DOX to confirm the conjugation as well as their properties including size and thermal stability. Using Ehrlich ascites carcinoma (EAC) cell line, the antitumor effect was evaluated by MTT assay in vitro and cell count; tumor cell cycle and apoptosis were evaluated by flow cytometry in vivo. The results showed that the loading percentages of DOX onto GO (GO/DOX) and GO/FA/DOX were 91% and 83%, respectively. TEM, FT-IR, and TGA confirmed the nano size, physical conjugation by shifted groups, and thermal stability. In vitro, the conjugates induced similar decrease of EAC cell viability, but still lower than those of free DOX. Treatment of EAC-bearing mice with GO/DOX or GO/FA/DOX forms induced significant decreases of the total numbers of EAC cells by 79% and 97%, respectively, as compared with free DOX (97%). DOX, GO/DOX, and GO/FA/DOX induced cell cycle arrest at G0, G1, and S phase, respectively. These conjugates also induced significant apoptosis with different profiles on viable, early, and late apoptotic EAC cells. In conclusion, loading DOX on GO nanosheet activated with FA can induce antitumor effect similar to those of free DOX but with different mechanisms.

氧化石墨烯（GO）纳米片由于其结构特性而成为药物输送系统，可以在叶酸（FA）存在的情况下得到增强。这项研究旨在比较GO作为被动形式（GO / DOX）和主动形式（GO / FA / DOX）递送阿霉素（DOX）的功效。在装载DOX之前和之后对这两种形式的结合物进行了表征，以确认结合以及它们的性质（包括尺寸和热稳定性）。使用艾氏腹水癌（EAC）细胞系，通过MTT法体外和细胞计数评估其抗肿瘤作用。通过体内流式细胞术评估肿瘤细胞周期和凋亡。结果表明，DOX在GO（GO / DOX）和GO / FA / DOX上的负载率分别为91％和83％。TEM，FT-IR和TGA证实了纳米尺寸，移位基团的物理共轭，。在体外，缀合物诱导了类似的EAC细胞活力降低，但仍低于游离DOX 。与游离DOX（97％）相比，用GO / DOX或GO / FA / DOX形式处理带有EAC的小鼠分别诱导EAC细胞总数分别显着减少79％和97％。DOX，GO / DOX和GO / FA / DOX分别导致细胞周期停滞在G0，G1和S期。这些缀合物还在存活的，早期和晚期的凋亡EAC细胞上诱导了具有不同谱的显着凋亡。总之，将DOX负载在用FA活化的GO纳米片上可以诱导类似于游离DOX的抗肿瘤作用，但机制不同。