Synergistic cytotoxicity effect of the combination of chitosan nanoencapsulated imatinib mesylate and quercetin in BCR-ABL positive K562 cells

Intolerable side effects and resistance to chemotherapeutic drugs have encouraged scientists to develop new methods of drug combinations with fewer complications. This study aimed to investigate the synergistic effects of quercetin and imatinib encapsulated in chitosan nanoparticles on cytotoxicity, apoptosis, and cell growth of the K562 cell line.

Imatinib and quercetin were encapsulated in chitosan nanoparticles and their physical properties were determined using standard methods and SEM microscope images. BCR-ABL positive K562 cells were cultured in a cell culture medium, cytotoxicity of drugs was determined by MTT assay and the effects of nano drugs on apoptosis in cells were investigated by Annexin V-FITC staining. The expression level of genes associated with apoptosis in cells was measured by real-time PCR. 

The IC50 for the combination of the nano drugs at 24 and 48 hr was 9.324 and 10.86 μg/ml, respectively. The data indicated that the encapsulated form of drugs induced apoptosis more effectively than the free form (P<0.05). Moreover, the synergistic effect of nano drugs in statistical analysis was proved (P=0.001). The combination of nano drugs resulted in the caspase 3, 8, and TP53 genes upregulation (P=0.001).

The results of the present study showed that the encapsulated form of imatinib and quercetin nano drugs with chitosan has more cytotoxicity than the free form of the drugs. In addition, the combination of imatinib and quercetin as a nano-drug complex has a synergistic effect on the induction of apoptosis in imatinib-resistant K562 cells.