Fan Lihong, Ge Hongyu, Zou Shengqiong, Xiao Yao, Wen Huigao, Li Ya, Feng Han, Nie Min
College of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Int J Biol Macromol. 2016 Dec;93(Pt A):582-590. doi: 10.1016/j.ijbiomac.2016.09.026. Epub 2016 Sep 9.
The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. The aim of this present study is to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release and targeted delivery. Graphene oxide (GO) was first prepared from purified natural graphite according to a modified Hummers' method. Then GO was functionalized with adipic acid dihydrazide to introduce amine groups, and sodium alginate (SA) was covalently conjugated to GO by the formation of amide bonds. The resulting GO-SA conjugate was characterized and used as a carrier to encapsulate the anticancer drug doxorubicin hydrochloride (DOX·HCl) to study in vitro release behavior. The maximum loading capacity of DOX on GO-SA was 1.843mg/mg and the drug release rate under tumor cell microenvironment of pH 5.0 was significantly higher than that under physiological conditions of pH 6.5 and 7.4. Methylthiazol tetrazolium (MTT) assay was applied to evaluate the Hela cells and NIH-3T3 cells cytotoxicity of GO-SA. Results showed that GO-SA had no obvious toxicity and GO-SA/DOX exhibits notable cytotoxicity to Hela cells. Cell uptake studies indicated that GO-SA could specifically transport the DOX into Hela cells over-expressing CD receptors and showed enhanced toxicity.
在过去几年中，包括药物递送在内的基于石墨烯的材料的生物医学应用迅速发展。本研究的目的是提高抗癌药物递送的效率和特异性，并实现智能控制释放和靶向递送。首先根据改良的Hummers方法从纯化的天然石墨制备氧化石墨烯（GO）。然后用己二酸二酰肼对GO进行功能化以引入胺基，并通过形成酰胺键将海藻酸钠（SA）与GO共价共轭。对所得的GO-SA缀合物进行表征，并用作载体来包封抗癌药物盐酸多柔比星（DOX·HCl）以研究体外释放行为。DOX在GO-SA上的最大负载量为1.843mg/mg，在pH 5.0的肿瘤细胞微环境下的药物释放速率明显高于在pH 6.5和7.4的生理条件下的释放速率。采用甲基噻唑四氮唑（MTT）法评估GO-SA对Hela细胞和NIH-3T3细胞的细胞毒性。结果表明，GO-SA没有明显毒性，而GO-SA/DOX对Hela细胞表现出显著的细胞毒性。细胞摄取研究表明，GO-SA可以将DOX特异性转运到过表达CD受体的Hela细胞中，并显示出增强的毒性。
