Ponto quântico de grafeno (Graphene Quantum Dot) decorado com imatinibe para o tratamento da leucemia

Abstract

Leukemia is a myeloproliferative disease characterized by symptoms such as anemia, weight loss, lethargy, and abnormal bleeding. Imatinib is one of the drugs used for treatment and targets the BCR-ABL protein, a tyrosine kinase that promotes the translocation of chromosomes 9 and 22. The treatment of leukemia has major challenges such as the high incidence of adverse effects and the lack of specificity of the drugs. Several studies have used nanoparticles, including graphene quantum dots (GQD) in chemotherapy drug delivery increasing specificity and decreased toxic effects. Therefore, this study aimed to associate imatinib with GQD forming the nanoparticle GQD@imatinibe to evaluate its activity in leukemic cells. Thus, GQD was synthesized and conjugated to imatinib by functionalization with carbodiimide. The association was confirmed by Fourier-transform infrared spectroscopy and toxicity was tested in cell lines (RPMI 8226 and NCI-ADR/RES). The induction of apoptosis was evaluated by flow cytometry and the diffusion of the conjugate through the cellular membrane was verified in MDA-MB-231 cells. Spectroscopy analyses showed the formation of new bands that correspond to the bond formed between imatinib and GQD, these datas corroborate by atomic force microscopy assay results. Cytotoxicity assay showed by the conjugate was lower than imatinib citotoxycity. GQD@imatinibe was able to cross the cell membrane and showed lower cellular toxicity in relation to imatinib. GQD showed the lowest toxicity, presenting safety to use in biological systems. Regarding the induction of apoptosis, cell apoptosis was observed in diferente percentagens in the cell treatment with imatinib and GQD@imatinibe. Therefore, The GQD proved to be safe in vitro and compatible to be associated with imatinib, in addition, GDQ@imatinibe is capable of reaching the intracellular medium and causing the death of leukemic cells.