期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 18, 期 46, 页码 14708-14716出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201200843
关键词
cancer; cytotoxicity; diazonium; drug delivery; graphene
资金
- NSFC [21033005]
- National Basic Research Program of China (973 Program) [2009CB930103]
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-C6H4-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.
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