Using magnetic nanoparticle supported drug in reducing multiple drug resistance in acute promyelocytic leukemia cell line (HL-60)

Cancer is an important health problem due to its high mortality rate and difficulties in treatment. Idarubicin is an anticancer drug frequently used in the treatment of breast cancer and acute leukemias. The use of idarubicin has some disadvantages. These are nonspecific to cancer cells, damage to healthy cells and tissues, recurrence of cancer after use, and development of multi-drug resistance. For this purpose, we used the magnetic nanoparticle (MNP) system, which will reduce drug resistance, ensure drug transport and make the drug more specific to leukemia cells. In our study, firstly, Fe3O4 nanoparticles were prepared, coated with various organic molecules, folic acid was attached to MNPs and characterization processes were performed with FT-IR, XRD, C-TEM, SEM methods, and idarubicin was bound. The cytotoxic effects of idarubicin-bound MNPs and free idarubicin on HL-60 cell lines were determined at 24, 48 and 72 hours by MTT and ATP tests, and IC50 values were calculated. The apoptosis status at the IC50 concentrations found was evaluated by flow cytometry, and the expression of MDR1, Puma, NOXA, BAX, Survivin and BCL-2 genes were measured by PCR method. In the cytotoxicity tests, it was found that the IC50 decreased between 2 and 20 times with the use of MNP, and the cytotoxic effect was further increased in folic acid-dependent MNPs. In gene expression measurements, it was found that the expressions of apoptotic genes increased, while the expressions of MDR1 and antiapoptotic genes were decreased in the use of MNP. Apoptosis was found to be increased in flow cytometry measurements. The use of MNP systems has reduced drug resistance since it provides controlled release of the drug and prevents its exit from the cell due to its structure. In addition, since it stimulated apoptosis, it enabled the drug to act at lower concentrations. The use of folic acid has increased the effectiveness of the drug, as it increases the specificity of the drug to cancer cells and facilitates entry into the cell. The results obtained here will shed light on further studies and will enable them to develop more effective methods for the treatment of cancer patients.