GO Nanosheets: Promising Nano Carrier for the S29, 1-(2-Chloro-2-(4-chlorophenyl-ethyl)-N-(4-fluorobenzyl)-1H-pyrazolo[3,4-d] pyrimidin-4-amine, Therapeutic Agent in Neuroblastoma

被引:0
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作者
Mardente, Stefania [1 ]
Aventaggiato, Michele [1 ]
Mari, Emanuela [1 ]
Francioso, Antonio [2 ]
Tafani, Marco [1 ]
Mosca, Luciana [2 ]
Zicari, Alessandra [1 ]
Malyshev, Igor [3 ]
Kuznetsova, Larisa [3 ]
Valentini, Federica [4 ]
机构
[1] Sapienza Univ Rome, Dept Expt Med, Viale Regina Elena 324, I-00161 Rome, Italy
[2] Sapienza Univ Rome, Dept Biochem Sci, Piazzale Aldo Moro 5, I-00161 Rome, Italy
[3] Moscow State Univ Med & Dent, Inst Gen Pathol & Pathophysiol, Baltijskaya St 8, Moscow 125315, Russia
[4] Tor Vergata Univ Rome, Dept Sci & Chem Technol, Via Ric Sci 1, I-000133 Rome, Italy
关键词
SRC family kinases; neuroblastoma; graphene oxide; ROS; cytotoxicity; SRC KINASE INHIBITORS; CELLULAR UPTAKE; TYROSINE KINASES; GRAPHENE OXIDE; NANOPARTICLES; METASTASIS; GROWTH;
D O I
10.3390/ijms21176430
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Graphene oxide (GO) derivatives are reported as a valid alternative to conventional carriers of therapeutic agents, because they have a large surface area, an excellent electrical and thermal conductivity and a great capacity for selective binding of drugs and therapeutics, due to the functionalization of their surfaces, edges and sides. In this work GO nanosheets, synthesized by electrochemical exfoliation of graphite (patent N 102015000023739, Tor Vergata University), were investigated as possible carriers of an anticancer drug, the S29, an inhibitor of a cytoplasmic tyrosine kinase (c-SRC) on a neuroblastoma cell line (SK N BE 2 cells). Neuroblastoma is a heterogenous tumor whose characteristics range from spontaneous regression to aggressive phenotypes that are due to different mutations that often occur in SRC family kinases. Inhibitors of tyrosine kinases are currently investigated for their anti-tumoral effects on aggressive neuroblastomas, but their uptake in cells and pharmacokinetics needs to be improved. In this work S29 was stably conjugated with highly water-dispersible GO nanoparticles. S29/GO complex formation was induced by 1h sonication and its stability was analyzed by chromatography coupled with spectrophotometry and mass spectrometry. The synthesized composite (GO-S29) was delivered into SK N BE 2 cells and its effects on cell viability, production of reactive oxygen species (ROS) and migration were studied. The results show that the compound GO-S29 exerts anti-tumoral effects on the neuroblastoma cell line, higher than both GO and S29 do alone and that GO has an additive effect on S29.
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页码:1 / 14
页数:14
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