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Covalent modification of reduced graphene oxide by means of diazonium chemistry and use as a drug-delivery system

机译:通过重氮化学对还原的氧化石墨烯进行共价改性,并用作药物递送系统

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Under acidic conditions, reduced graphene oxide (rGO) was functionalized with p-aminobenzoic acid, which formed the diazonium ions through the diazotization with a wet-chemical method. Surfactants or stabilizers were not applied during the diazotization. After the functionalized rGO was treated through mild sonication in aqueous solution, these functionalized rGO sheets were less than two layers, which was determined by atomic force microscopy (AFM) imaging. The water solubility of functionalized rGO after the introduction of polyethyleneimine (PEI) was improved significantly; it was followed by covalent binding of folic acid (FA) molecules to the functionalized rGO to allow us to specifically target CBRH7919 cancer cells by using FA as a receptor. The loading and release behaviors of elsinochrome A (EA) and doxorubicin (DOX) on the functionalized rGO sheets were investigated. The EA loading ratio onto rGO-C_6H_4-CO-NH-PEI-NH-CO-FA (abbreviated rGO-PEI-FA, the weight ratio of drug loaded onto rGO-PEI-FA) was approximately 45.56 %, and that of DOX was approximately 28.62 %. It was interesting that the drug release from rGO-PEI-FA was pH- and salt-dependent. The results of cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM) assays, as well as cell morphology observations) clearly showed that the concentration of rGO-PEI-FA as the drug-delivery composite should be less than 12.5 mg L~(-1). The conjugation of DOX and rGO-PEI-FA can enhance the cancer-cell apoptosis effectively and can also push the cancer cells to the vulnerable G2 phase of the cell cycle, which is most sensitive and susceptible to damage by drugs or radiation. New horizons: A novel method for covalent modification of reduced graphene oxide (rGO) by means of diazonium chemistry was developed. The functionalized-rGO drug-delivery system was tested for the first time (see scheme) and provided a new vision for functionalizing rGO and studying drug-delivery systems based on graphene materials.
机译:在酸性条件下,还原的氧化石墨烯(rGO)用对氨基苯甲酸官能化,通过湿化学方法通过重氮化反应形成重氮离子。在重氮化过程中不使用表面活性剂或稳定剂。在水溶液中通过温和超声处理功能化的rGO后,这些功能化的rGO片少于两层,这是通过原子力显微镜(AFM)成像确定的。引入聚乙烯亚胺(PEI)后,功能化rGO的水溶性显着提高;随后是叶酸(FA)分子与功能化rGO的共价结合,从而使我们能够以FA为受体,特异性靶向CBRH7919癌细胞。研究了在功能化的rGO片材上的elinochrome A(EA)和阿霉素(DOX)的负载和释放行为。 EA在rGO-C_6H_4-CO-NH-PEI-NH-CO-FA上的负载率(rGO-PEI-FA的缩写,药物在rGO-PEI-FA上的重量比)约为45.56%,DOX约为28.62%。有趣的是,rGO-PEI-FA释放的药物是pH和盐依赖性的。细胞毒性结果(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)和流式细胞仪(FCM)分析以及细胞形态观察)清楚地表明rGO的浓度-PEI-FA作为药物传递复合物应小于12.5 mg L〜(-1)。 DOX和rGO-PEI-FA的结合可以有效地增强癌细胞的凋亡,也可以将癌细胞推向细胞周期的易受伤害的G2期,该期最敏感,最容易受到药物或放射线的破坏。新视野:开发了一种通过重氮化学共价修饰还原氧化石墨烯(rGO)的新方法。首次对功能化的rGO药物递送系统进行了测试(请参阅计划),并为功能化rGO和研究基于石墨烯材料的药物递送系统提供了新的视野。

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